Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay
Identifieur interne : 000506 ( Istex/Corpus ); précédent : 000505; suivant : 000507Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay
Auteurs : Jon C. Mirsalis ; C. Kim Tyson ; Byron E. ButterworthSource :
- Environmental Mutagenesis [ 0192-2521 ] ; 1982.
English descriptors
- Teeft :
- Assay, Bermudez, Butterworth, Carcinogen, Chemical carcinogens, Chemical industry institute, Dmso, Environ mutagen, Final concentration, Flow labs, Genotoxic, Genotoxic agents, Genotoxic carcinogens, Genotoxic hepatocarcinogens, Genotoxicity, Hepatocyte, Hepatocytes, High degree, Iarc monographs, Menlo park, Metabolic activation, Mirsalis, Mirsalisand butterworth, Mutagen, Mutagen mnng, Other compounds, Pancreatic carcinogen azaserine, Peak response, Potent hepatocarcinogen, Potential carcinogens, Relevant information, Repair assay, Safrole, Sigma chemical, Significant elevations, Small number, Small percentage, Standard errors, Time course, Unscheduled, Vivo treatment, Weak hepatocarcinogen safrole, Whole animal.
Abstract
The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with 3H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B1, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is valuable for the detection and study of a variety of genotoxic carcinogens.
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DOI: 10.1002/em.2860040506
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Kim Tyson</name><affiliation><mods:affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</mods:affiliation></affiliation></author><author><name sortKey="Butterworth, Byron E" sort="Butterworth, Byron E" uniqKey="Butterworth B" first="Byron E." last="Butterworth">Byron E. Butterworth</name><affiliation><mods:affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Environmental Mutagenesis</title><title level="j" type="alt">ENVIRONMENTAL MUTAGENESIS</title><idno type="ISSN">0192-2521</idno><idno type="eISSN">1930-238X</idno><imprint><biblScope unit="vol">4</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="553">553</biblScope><biblScope unit="page" to="562">562</biblScope><biblScope unit="page-count">10</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>New York</pubPlace><date type="published" when="1982">1982</date></imprint><idno type="ISSN">0192-2521</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0192-2521</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Assay</term><term>Bermudez</term><term>Butterworth</term><term>Carcinogen</term><term>Chemical carcinogens</term><term>Chemical industry institute</term><term>Dmso</term><term>Environ mutagen</term><term>Final concentration</term><term>Flow labs</term><term>Genotoxic</term><term>Genotoxic agents</term><term>Genotoxic carcinogens</term><term>Genotoxic hepatocarcinogens</term><term>Genotoxicity</term><term>Hepatocyte</term><term>Hepatocytes</term><term>High degree</term><term>Iarc monographs</term><term>Menlo park</term><term>Metabolic activation</term><term>Mirsalis</term><term>Mirsalisand butterworth</term><term>Mutagen</term><term>Mutagen mnng</term><term>Other compounds</term><term>Pancreatic carcinogen azaserine</term><term>Peak response</term><term>Potent hepatocarcinogen</term><term>Potential carcinogens</term><term>Relevant information</term><term>Repair assay</term><term>Safrole</term><term>Sigma chemical</term><term>Significant elevations</term><term>Small number</term><term>Small percentage</term><term>Standard errors</term><term>Time course</term><term>Unscheduled</term><term>Vivo treatment</term><term>Weak hepatocarcinogen safrole</term><term>Whole animal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with 3H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B1, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is valuable for the detection and study of a variety of genotoxic carcinogens.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>mirsalis</json:string><json:string>butterworth</json:string><json:string>carcinogen</json:string><json:string>genotoxic</json:string><json:string>assay</json:string><json:string>hepatocyte</json:string><json:string>genotoxicity</json:string><json:string>repair assay</json:string><json:string>mutagen</json:string><json:string>hepatocytes</json:string><json:string>unscheduled</json:string><json:string>safrole</json:string><json:string>bermudez</json:string><json:string>dmso</json:string><json:string>peak response</json:string><json:string>metabolic activation</json:string><json:string>iarc monographs</json:string><json:string>environ mutagen</json:string><json:string>whole animal</json:string><json:string>chemical carcinogens</json:string><json:string>genotoxic agents</json:string><json:string>genotoxic carcinogens</json:string><json:string>sigma chemical</json:string><json:string>flow labs</json:string><json:string>genotoxic hepatocarcinogens</json:string><json:string>relevant information</json:string><json:string>pancreatic carcinogen azaserine</json:string><json:string>other compounds</json:string><json:string>time course</json:string><json:string>standard errors</json:string><json:string>menlo park</json:string><json:string>significant elevations</json:string><json:string>mutagen mnng</json:string><json:string>potential carcinogens</json:string><json:string>mirsalisand butterworth</json:string><json:string>vivo treatment</json:string><json:string>final concentration</json:string><json:string>potent hepatocarcinogen</json:string><json:string>chemical industry institute</json:string><json:string>small number</json:string><json:string>high degree</json:string><json:string>weak hepatocarcinogen safrole</json:string><json:string>small percentage</json:string></teeft></keywords><author><json:item><name>Dr. Jon C. Mirsalis</name><affiliations><json:string>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</json:string><json:string>Current Address: SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</json:string><json:string>Correspondence address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025</json:string></affiliations></json:item><json:item><name>C. Kim Tyson</name><affiliations><json:string>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</json:string><json:string>Current Address: SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</json:string></affiliations></json:item><json:item><name>Byron E. Butterworth</name><affiliations><json:string>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>in vivo genotoxicity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>hepatocarcinogenesis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>unscheduled DNA synthesis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DNA repair</value></json:item></subject><articleId><json:string>EM2860040506</json:string></articleId><arkIstex>ark:/67375/WNG-3S4730KF-F</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with 3H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B1, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. 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Induction</json:string><json:string>Kim Tyson</json:string><json:string>Safrole</json:string><json:string>Variation</json:string><json:string>Jack H. Frost</json:string><json:string>Mayo Smith</json:string></persName><placeName><json:string>Rochester</json:string><json:string>Columbia</json:string><json:string>NY</json:string><json:string>Milwaukee</json:string><json:string>Pittsburgh</json:string><json:string>Sendai</json:string><json:string>SC</json:string><json:string>Ldolla</json:string><json:string>CA</json:string><json:string>Kingston</json:string><json:string>WI</json:string><json:string>PA</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>San and Stich, 1975</json:string><json:string>Langenbach et al, 19811</json:string><json:string>Trosko and Yager, 1974</json:string><json:string>Martin et al, 1978</json:string><json:string>Petzold and Swenberg, 19781</json:string><json:string>Mirsalis and Butterworth, 19821</json:string><json:string>Wislocki et al, 19771</json:string><json:string>Bond et al, 19811</json:string><json:string>Probst et al, 19811</json:string><json:string>Ito et al, 19691</json:string><json:string>Mirsalis et al, 19821</json:string><json:string>Parodi et al, 19811</json:string><json:string>Tsuda et al, 19801</json:string><json:string>Bermudez et al, 19821</json:string><json:string>Martin et al, 19781</json:string><json:string>Bermudez et al, 1979</json:string><json:string>Flaks and Nicoll, 19751</json:string><json:string>Kligerman et al, 19811</json:string><json:string>Mirsalis and Butterworth, 19801</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-3S4730KF-F</json:string></ark><categories><wos></wos><scienceMetrix></scienceMetrix><scopus><json:string>1 - Physical Sciences</json:string><json:string>2 - Environmental Science</json:string><json:string>3 - Health, Toxicology and Mutagenesis</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Genetics</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1982</publicationDate><copyrightDate>1982</copyrightDate><doi><json:string>10.1002/em.2860040506</json:string></doi><id>E18F2442B743518F706EB2AC39FAB9B1466D907A</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-3S4730KF-F/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-3S4730KF-F/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/WNG-3S4730KF-F/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay</title><title level="a" type="short" xml:lang="en">In Vivo‐In Vitro DNA Repair Assay</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>New York</pubPlace><availability><licence>Copyright © 1982 Wiley‐Liss, Inc., A Wiley Company</licence></availability><date type="published" when="1982"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main">Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay</title><title level="a" type="short" xml:lang="en">In Vivo‐In Vitro DNA Repair Assay</title><author xml:id="author-0000" role="corresp"><persName><addName>Dr.</addName><forename type="first">Jon C.</forename><surname>Mirsalis</surname></persName><affiliation><orgName type="institution">Chemical Industry Institute of Toxicology</orgName><orgName type="laboratory">Research Triangle Park</orgName><address><addrLine>North Carolina</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation><affiliation><address><addrLine>SRI International</addrLine><addrLine>Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</addrLine></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">C. Kim</forename><surname>Tyson</surname></persName><affiliation><orgName type="institution">Chemical Industry Institute of Toxicology</orgName><orgName type="laboratory">Research Triangle Park</orgName><address><addrLine>North Carolina</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation><affiliation><address><addrLine>SRI International</addrLine><addrLine>Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</addrLine></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Byron E.</forename><surname>Butterworth</surname></persName><affiliation><orgName type="institution">Chemical Industry Institute of Toxicology</orgName><orgName type="laboratory">Research Triangle Park</orgName><address><addrLine>North Carolina</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><idno type="istex">E18F2442B743518F706EB2AC39FAB9B1466D907A</idno><idno type="ark">ark:/67375/WNG-3S4730KF-F</idno><idno type="DOI">10.1002/em.2860040506</idno><idno type="unit">EM2860040506</idno><idno type="toTypesetVersion">file:EM.EM2860040506.pdf</idno></analytic><monogr><title level="j" type="main">Environmental Mutagenesis</title><title level="j" type="alt">ENVIRONMENTAL MUTAGENESIS</title><idno type="pISSN">0192-2521</idno><idno type="eISSN">1930-238X</idno><idno type="book-DOI">10.1002/(ISSN)1930-238X</idno><idno type="book-part-DOI">10.1002/em.v4:5</idno><idno type="product">EMBACK</idno><imprint><biblScope unit="vol">4</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="553">553</biblScope><biblScope unit="page" to="562">562</biblScope><biblScope unit="page-count">10</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>New York</pubPlace><date type="published" when="1982"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.10" when="2019-12-20"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with <hi rend="superscript">3</hi>H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B<hi rend="subscript">1</hi>, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is valuable for the detection and study of a variety of genotoxic carcinogens.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">in vivo genotoxicity</term><term xml:id="kwd2">hepatocarcinogenesis</term><term xml:id="kwd3">unscheduled DNA synthesis</term><term xml:id="kwd4">DNA repair</term></keywords><keywords rend="articleCategory"><term>Research Paper</term></keywords><keywords rend="tocHeading1"><term>Research Papers</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-3S4730KF-F/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>New York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1930-238X</doi><issn type="print">0192-2521</issn><issn type="electronic">1930-238X</issn><idGroup><id type="product" value="EMBACK"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ENVIRONMENTAL MUTAGENESIS">Environmental Mutagenesis</title><title type="short">Environ. mutagen</title></titleGroup></publicationMeta><publicationMeta level="part" position="50"><doi origin="wiley" registered="yes">10.1002/em.v4:5</doi><numberingGroup><numbering type="journalVolume" number="4">4</numbering><numbering type="journalIssue">5</numbering></numberingGroup><coverDate startDate="1982">1982</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley" registered="yes">10.1002/em.2860040506</doi><idGroup><id type="unit" value="EM2860040506"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="articleCategory">Research Paper</title><title type="tocHeading1">Research Papers</title></titleGroup><copyright ownership="publisher">Copyright © 1982 Wiley‐Liss, Inc., A Wiley Company</copyright><eventGroup><event type="manuscriptReceived" date="1982-01-05"></event><event type="manuscriptRevised" date="1982-04-25"></event><event type="manuscriptAccepted" date="1982-04-25"></event><event type="firstOnline" date="2006-07-14"></event><event type="publishedOnlineFinalForm" date="2006-07-14"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-24"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst">553</numbering><numbering type="pageLast">562</numbering></numberingGroup><correspondenceTo>SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:EM.EM2860040506.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="23"></count></countGroup><titleGroup><title type="main" xml:lang="en">Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay</title><title type="short" xml:lang="en">In Vivo‐In Vitro DNA Repair Assay</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" currentRef="#curr1" corresponding="yes"><personName><honorifics>Dr.</honorifics><givenNames>Jon C.</givenNames><familyName>Mirsalis</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1" currentRef="#curr1"><personName><givenNames>C. Kim</givenNames><familyName>Tyson</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Byron E.</givenNames><familyName>Butterworth</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</unparsedAffiliation></affiliation><affiliation xml:id="curr1"><unparsedAffiliation>SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">in vivo genotoxicity</keyword><keyword xml:id="kwd2">hepatocarcinogenesis</keyword><keyword xml:id="kwd3">unscheduled DNA synthesis</keyword><keyword xml:id="kwd4">DNA repair</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with <sup>3</sup>H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B<sub>1</sub>, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is valuable for the detection and study of a variety of genotoxic carcinogens.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>In Vivo‐In Vitro DNA Repair Assay</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Detection of genotoxic carcinogens in the in vivo‐in vitro hepatocyte dna repair assay</title></titleInfo><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="given">Jon C.</namePart><namePart type="family">Mirsalis</namePart><affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</affiliation><affiliation>Current Address: SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</affiliation><affiliation>Correspondence address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C. Kim</namePart><namePart type="family">Tyson</namePart><affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</affiliation><affiliation>Current Address: SRI International, Biochemical Genetics Department, 333 Ravenswood Ave, Menlo Park, CA 94025</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Byron E.</namePart><namePart type="family">Butterworth</namePart><affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1982</dateIssued><dateCaptured encoding="w3cdtf">1982-01-05</dateCaptured><dateValid encoding="w3cdtf">1982-04-25</dateValid><copyrightDate encoding="w3cdtf">1982</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">2</extent><extent unit="references">23</extent></physicalDescription><abstract lang="en">The in vivo‐in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of compounds from a wide variety of structural classes. Male Fischer‐344 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with 3H‐thymidine. Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); ≥ 5 NG was considered positive. Water, corn oil, or DMSO controls produced ‐3 to ‐6 NG with ≤ 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of > 15 NG including dimethylnitrosamine, 2‐acetylaminofluorene (2‐AAF), azoxymethane, 1,2‐dimethylhydrazine, benzidine, aflatoxin B1, 2,6‐dinitrotoluene, and 2,4‐diaminotoluene. The noncarcinogen, 2,6‐diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12‐dimethylbenzen(a)anthracene yielded from ‐2 to ‐4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2‐AAF did not induce its maximum response until 12 hr post‐treatment. The potent hepatotoxin carbon tetrachloride induced a 40‐fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post‐treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that is is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is valuable for the detection and study of a variety of genotoxic carcinogens.</abstract><subject lang="en"><genre>keywords</genre><topic>in vivo genotoxicity</topic><topic>hepatocarcinogenesis</topic><topic>unscheduled DNA synthesis</topic><topic>DNA repair</topic></subject><relatedItem type="host"><titleInfo><title>Environmental Mutagenesis</title></titleInfo><titleInfo type="abbreviated"><title>Environ. mutagen</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Research Paper</topic><topic>Research Papers</topic></subject><identifier type="ISSN">0192-2521</identifier><identifier type="eISSN">1930-238X</identifier><identifier type="DOI">10.1002/(ISSN)1930-238X</identifier><identifier type="PublisherID">EMBACK</identifier><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>4</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>553</start><end>562</end><total>10</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit1"><titleInfo><title>Drug‐resistant lymphocytes in man as indicators of somatic cell mutation</title></titleInfo><name type="personal"><namePart type="given">RJ</namePart><namePart type="family">Albertini</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Albertini RJ (1980): Drug‐resistant lymphocytes in man as indicators of somatic cell mutation. Teratogen, Carcinogen, Mutagen 1: 25–48.</note><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>25</start><end>48</end></extent></part><relatedItem type="host"><titleInfo><title>Teratogen, Carcinogen, Mutagen</title></titleInfo><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>25</start><end>48</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit2"><titleInfo><title>The effect of 2,4‐diaminotoluene and isomers of dinitro‐toluene on unscheduled DNA synthesis in primary rat hepatocytes</title></titleInfo><name type="personal"><namePart type="given">E</namePart><namePart type="family">Bermudez</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Tillery</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BE</namePart><namePart type="family">Butterworth</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Bermudez E, Tillery D, Butterworth BE (1979): The effect of 2,4‐diaminotoluene and isomers of dinitro‐toluene on unscheduled DNA synthesis in primary rat hepatocytes. Environ Mutagen 1: 391–398.</note><part><date>1979</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>391</start><end>398</end></extent></part><relatedItem type="host"><titleInfo><title>Environ Mutagen</title></titleInfo><part><date>1979</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>391</start><end>398</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit3"><titleInfo><title>The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the Chinese hamster ovary/hypoxanthine‐guanine phosphoribosyl transferase mutational assay</title></titleInfo><name type="personal"><namePart type="given">E</namePart><namePart type="family">Bermudez</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">DB</namePart><namePart type="family">Couch</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Tillery</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Bermudez E, Couch DB, Tillery D (1982): The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the Chinese hamster ovary/hypoxanthine‐guanine phosphoribosyl transferase mutational assay. Environ Mutagen 4: 55–64.</note><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>4</number></detail><extent unit="pages"><start>55</start><end>64</end></extent></part><relatedItem type="host"><titleInfo><title>Environ Mutagen</title></titleInfo><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>4</number></detail><extent unit="pages"><start>55</start><end>64</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit4"><titleInfo><title>Fund Appl Toxicol</title></titleInfo><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Bond</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JP</namePart><namePart type="family">Chism</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">DE</namePart><namePart type="family">Rickert</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Popp</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>other</genre><part><date>1981</date></part></relatedItem><relatedItem type="references" displayLabel="cit5"><titleInfo><title>Chemical Industry Institute of Toxicology(1978):A 24‐month toxicology study in Fischer‐344 rats given dinitrotoluene, 12‐month report, Docket 327N8.</title></titleInfo><name type="corporate"><namePart>Chemical Industry Institute of Toxicology</namePart></name><genre>other</genre><part><date>1978</date></part></relatedItem><relatedItem type="references" displayLabel="cit6"><titleInfo><title>Modification of toxic liver injury in the rat II. Protective effect of cycloheximide on ethionine‐induced damage and autoprotective effects of high doses of ethionine, 3′‐methyl‐4‐dimethylaminoazobenzene, and 2‐acetylaminofluorene</title></titleInfo><name type="personal"><namePart type="given">B</namePart><namePart type="family">Flaks</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JW</namePart><namePart type="family">Nicoll</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Flaks B, Nicoll JW (1975): Modification of toxic liver injury in the rat II. Protective effect of cycloheximide on ethionine‐induced damage and autoprotective effects of high doses of ethionine, 3′‐methyl‐4‐dimethylaminoazobenzene, and 2‐acetylaminofluorene. Toxicol Appl Pharmacol 32: 603–620.</note><part><date>1975</date><detail type="volume"><caption>vol.</caption><number>32</number></detail><extent unit="pages"><start>603</start><end>620</end></extent></part><relatedItem type="host"><titleInfo><title>Toxicol Appl Pharmacol</title></titleInfo><part><date>1975</date><detail type="volume"><caption>vol.</caption><number>32</number></detail><extent unit="pages"><start>603</start><end>620</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit7"><titleInfo><title>IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man.Vols 1–13(1972–1974)International Agency for Research on Cancer,Lyon, France.</title></titleInfo><note type="citation/reference">IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Vols 1–13 (1972 –1974) International Agency for Research on Cancer, Lyon, France.</note><genre>book</genre><originInfo><publisher>International Agency for Research on Cancer</publisher><place><placeTerm type="text">Lyon, France</placeTerm></place></originInfo><part><date>1972</date><detail type="volume"><caption>vol.</caption><number>1–13</number></detail></part></relatedItem><relatedItem type="references" displayLabel="cit8"><titleInfo><title>The development of carcinoma in liver of rats treated with m‐toluylenediamine and the synergistic and antagonistic effects with other chemicals</title></titleInfo><name type="personal"><namePart type="given">N</namePart><namePart type="family">Ito</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Y</namePart><namePart type="family">Hiasa</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Y</namePart><namePart type="family">Konishi</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Marugami</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Ito N, Hiasa Y, Konishi Y, Marugami M (1969): The development of carcinoma in liver of rats treated with m‐toluylenediamine and the synergistic and antagonistic effects with other chemicals. Cancer Res 29: 1137–1145.</note><part><date>1969</date><detail type="volume"><caption>vol.</caption><number>29</number></detail><extent unit="pages"><start>1137</start><end>1145</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1969</date><detail type="volume"><caption>vol.</caption><number>29</number></detail><extent unit="pages"><start>1137</start><end>1145</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit9"><titleInfo><title>Characterization of a rat lymphocyte culture system for assessing sister‐chromatid exchange after in vivo exposure to genotoxic agents</title></titleInfo><name type="personal"><namePart type="given">AD</namePart><namePart type="family">Kligerman</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JL</namePart><namePart type="family">Wilmer</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">GL</namePart><namePart type="family">Erexson</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Kligerman AD, Wilmer JL, Erexson GL (1981): Characterization of a rat lymphocyte culture system for assessing sister‐chromatid exchange after in vivo exposure to genotoxic agents. Environ Mutagen 3: 531–543.</note><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>531</start><end>543</end></extent></part><relatedItem type="host"><titleInfo><title>Environ Mutagen</title></titleInfo><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>531</start><end>543</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit10"><titleInfo><title>Lung and liver cell‐mediated mutagenesis systems: specificities in the activation of chemical carcinogens</title></titleInfo><name type="personal"><namePart type="given">R</namePart><namePart type="family">Langenbach</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Nesnow</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Tompa</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Gingell</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Kuszynski</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Langenbach R, Nesnow S, Tompa A, Gingell R, Kuszynski C (1981): Lung and liver cell‐mediated mutagenesis systems: specificities in the activation of chemical carcinogens. Carcinogenesis 2: 851–858.</note><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>2</number></detail><extent unit="pages"><start>851</start><end>858</end></extent></part><relatedItem type="host"><titleInfo><title>Carcinogenesis</title></titleInfo><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>2</number></detail><extent unit="pages"><start>851</start><end>858</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit11"><titleInfo><title>Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells</title></titleInfo><name type="personal"><namePart type="given">CN</namePart><namePart type="family">Martin</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">AC</namePart><namePart type="family">McDermid</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RC</namePart><namePart type="family">Garner</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Martin CN, McDermid AC, Garner RC (1978): Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res 38: 2621–2627.</note><part><date>1978</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>2621</start><end>2627</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1978</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>2621</start><end>2627</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit12"><titleInfo><title>Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: An in vivo‐in vitro assay for potential carcinogens and mutagens</title></titleInfo><name type="personal"><namePart type="given">JC</namePart><namePart type="family">Mirsalis</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BE</namePart><namePart type="family">Butterworth</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Mirsalis JC, Butterworth BE (1980): Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: An in vivo‐in vitro assay for potential carcinogens and mutagens. Carcinogenesis 1: 621–625.</note><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>621</start><end>625</end></extent></part><relatedItem type="host"><titleInfo><title>Carcinogenesis</title></titleInfo><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>1</number></detail><extent unit="pages"><start>621</start><end>625</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit13"><titleInfo><title>Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene</title></titleInfo><name type="personal"><namePart type="given">JC</namePart><namePart type="family">Mirsalis</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BE</namePart><namePart type="family">Butterworth</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Mirsalis JC, Butterworth BE (1982): Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene. Carcinogenesis 3: 241–245.</note><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>241</start><end>245</end></extent></part><relatedItem type="host"><titleInfo><title>Carcinogenesis</title></titleInfo><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>241</start><end>245</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit14"><titleInfo><title>The role of gut flora in the genotoxicity of dintrotoluene</title></titleInfo><name type="personal"><namePart type="given">JC</namePart><namePart type="family">Mirsalis</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">TE</namePart><namePart type="family">Hamm Jr</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JM</namePart><namePart type="family">Sherrill</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BE</namePart><namePart type="family">Butterworth</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Mirsalis JC, Hamm TE, Jr, Sherrill JM, Butterworth BE (1982): The role of gut flora in the genotoxicity of dintrotoluene. Nature 295: 322–323.</note><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>295</number></detail><extent unit="pages"><start>322</start><end>323</end></extent></part><relatedItem type="host"><titleInfo><title>Nature</title></titleInfo><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>295</number></detail><extent unit="pages"><start>322</start><end>323</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit15"><titleInfo><title>Bioassay of 2,6‐toluenediamine dihydrochloride for possible carcino‐genicity</title></titleInfo><name type="corporate"><namePart>National Cancer Institute</namePart></name><genre>journal-article</genre><note type="citation/reference">National Cancer Institute (1980): Bioassay of 2,6‐toluenediamine dihydrochloride for possible carcino‐genicity. Gov Rep Announce Index (US) 80: 5297.</note><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>80</number></detail><extent unit="pages"><start>5297</start></extent></part><relatedItem type="host"><titleInfo><title>Gov Rep Announce Index (US)</title></titleInfo><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>80</number></detail><extent unit="pages"><start>5297</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit16"><titleInfo><title>Alkaline DNA fragmentation in vivo: Borderline or negative results obtained, respectively, with 7,12‐dimethylbenz(a)anthracene and benzo(a)pyrene</title></titleInfo><name type="personal"><namePart type="given">S</namePart><namePart type="family">Parodi</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Taningher</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Pala</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Santi</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Parodi S, Taningher M, Pala M, Santi L (1981): Alkaline DNA fragmentation in vivo: Borderline or negative results obtained, respectively, with 7,12‐dimethylbenz(a)anthracene and benzo(a)pyrene. Tumori 67: 87–93.</note><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>67</number></detail><extent unit="pages"><start>87</start><end>93</end></extent></part><relatedItem type="host"><titleInfo><title>Tumori</title></titleInfo><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>67</number></detail><extent unit="pages"><start>87</start><end>93</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit17"><titleInfo><title>Detection of DNA damage induced in vivo following exposure of rats to carcinogens</title></titleInfo><name type="personal"><namePart type="given">GP</namePart><namePart type="family">Petzold</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Swenberg</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Petzold GP, Swenberg JA (1978): Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Res 38: 1589–1594.</note><part><date>1978</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>1589</start><end>1594</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1978</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>1589</start><end>1594</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit18"><titleInfo><title>Chemically induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds</title></titleInfo><name type="personal"><namePart type="given">GS</namePart><namePart type="family">Probst</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RE</namePart><namePart type="family">McMahon</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">LE</namePart><namePart type="family">Hill</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">CZ</namePart><namePart type="family">Thompson</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JK</namePart><namePart type="family">Epp</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">SB</namePart><namePart type="family">Neal</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Probst GS, McMahon RE, Hill LE, Thompson CZ, Epp JK, Neal SB (1981): Chemically induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds. Environ Mutagen 3: 11–32.</note><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>11</start><end>32</end></extent></part><relatedItem type="host"><titleInfo><title>Environ Mutagen</title></titleInfo><part><date>1981</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>11</start><end>32</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit19"><titleInfo><title>DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens</title></titleInfo><name type="personal"><namePart type="given">RHC</namePart><namePart type="family">San</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">HF</namePart><namePart type="family">Stich</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">San RHC, Stich HF (1975): DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens. Int J Cancer 16: 284–291.</note><part><date>1975</date><detail type="volume"><caption>vol.</caption><number>16</number></detail><extent unit="pages"><start>284</start><end>291</end></extent></part><relatedItem type="host"><titleInfo><title>Int J Cancer</title></titleInfo><part><date>1975</date><detail type="volume"><caption>vol.</caption><number>16</number></detail><extent unit="pages"><start>284</start><end>291</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit20"><titleInfo><title>A sensitive method to measure physical and chemical carcinogen‐induced “unscheduled DNA synthesis” in rapidly dividing eukaryotic cells</title></titleInfo><name type="personal"><namePart type="given">JE</namePart><namePart type="family">Trosko</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JD</namePart><namePart type="family">Yager</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Trosko JE, Yager JD (1974): A sensitive method to measure physical and chemical carcinogen‐induced “unscheduled DNA synthesis” in rapidly dividing eukaryotic cells. Exp Cell Res 88: 47–55.</note><part><date>1974</date><detail type="volume"><caption>vol.</caption><number>88</number></detail><extent unit="pages"><start>47</start><end>55</end></extent></part><relatedItem type="host"><titleInfo><title>Exp Cell Res</title></titleInfo><part><date>1974</date><detail type="volume"><caption>vol.</caption><number>88</number></detail><extent unit="pages"><start>47</start><end>55</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit21"><titleInfo><title>Induction of resistant hepatocytes as a new principle for a possible short‐term in vivo test for carcinogens</title></titleInfo><name type="personal"><namePart type="given">H</namePart><namePart type="family">Tsuda</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">Lee</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Farber</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Tsuda H, Lee G, Farber E (1980): Induction of resistant hepatocytes as a new principle for a possible short‐term in vivo test for carcinogens. Cancer Res 40: 1157–1164.</note><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>40</number></detail><extent unit="pages"><start>1157</start><end>1164</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1980</date><detail type="volume"><caption>vol.</caption><number>40</number></detail><extent unit="pages"><start>1157</start><end>1164</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit22"><titleInfo><title>Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures</title></titleInfo><name type="personal"><namePart type="given">GM</namePart><namePart type="family">Williams</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Williams GM (1977): Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res 37: 1845–1851.</note><part><date>1977</date><detail type="volume"><caption>vol.</caption><number>37</number></detail><extent unit="pages"><start>1845</start><end>1851</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1977</date><detail type="volume"><caption>vol.</caption><number>37</number></detail><extent unit="pages"><start>1845</start><end>1851</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit23"><titleInfo><title>Carcinogenic and mutagenic activities of safrole, 1′‐hydroxysafrole, and some known or possible metabolites</title></titleInfo><name type="personal"><namePart type="given">PG</namePart><namePart type="family">Wislocki</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">EC</namePart><namePart type="family">Miller</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Miller</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">EC</namePart><namePart type="family">McCoy</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">HS</namePart><namePart type="family">Rosenkranz</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Wislocki PG, Miller, EC, Miller JA, McCoy EC, Rosenkranz HS (1977): Carcinogenic and mutagenic activities of safrole, 1′‐hydroxysafrole, and some known or possible metabolites. Cancer Res 37: 1883–1891.</note><part><date>1977</date><detail type="volume"><caption>vol.</caption><number>37</number></detail><extent unit="pages"><start>1883</start><end>1891</end></extent></part><relatedItem type="host"><titleInfo><title>Cancer Res</title></titleInfo><part><date>1977</date><detail type="volume"><caption>vol.</caption><number>37</number></detail><extent unit="pages"><start>1883</start><end>1891</end></extent></part></relatedItem></relatedItem><identifier type="istex">E18F2442B743518F706EB2AC39FAB9B1466D907A</identifier><identifier type="ark">ark:/67375/WNG-3S4730KF-F</identifier><identifier type="DOI">10.1002/em.2860040506</identifier><identifier type="ArticleID">EM2860040506</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1982 Wiley‐Liss, Inc., A Wiley Company</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>Converted from (version ) to MODS version 3.6.</recordOrigin><recordCreationDate encoding="w3cdtf">2019-11-14</recordCreationDate></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-3S4730KF-F/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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