Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene
Identifieur interne : 000707 ( Istex/Corpus ); précédent : 000706; suivant : 000708Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene
Auteurs : Jon C. Mirsalis ; Byron E. ButterworthSource :
- Carcinogenesis [ 0143-3334 ] ; 1982.
Abstract
The purpose of this study was to examine the induction of unscheduled DNA synthesis (UDS) by the potent hepatocarcinogen technical grade dinitrotoluene (tgDNT; 76% 2, 4-DNT, 19% 2, 6-DNT) using the in vivo-in vitro hepatocyte DNA repair assay. Male Fischer-344 rats were treated by gavage and hepatocytes were isolated by liver perfusion and cultured with [3H]thymidine. UDS was measured by quantitative autoradiography as net grains/nucleus (NG); ≥5 NG was considered positive. Controls consistently had − 3 to − 6 NG. A dose-related increase in UDS was observed 12 h after treatment, with 200 mg/kg tgDNT producing 26 NG. A 50-fold increase in the number of cells in S-phase was observed at 48 h after treatment. This increase in S-phase cells could be suppressed in the presence of 10–20 mM hydroxyurea (HU), while the same levels of HU did not affect the level of UDS at 12 h after treatment. 2, 4-DNT produced only a weak response, in contrast to 2, 6-DNT which was a potent inducer of UDS. Treatment of female rats with tgDNT yielded only modest increases in UDS and DNA replication relative to males. These results are consistent with the carcinogenicity studies and indicate that tgDNT is a potent genotoxic agent, with 2, 6-DNT contributing the major portion of the effect.
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DOI: 10.1093/carcin/3.3.241
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Mirsalis</name><affiliation><mods:affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</mods:affiliation></affiliation><affiliation><mods:affiliation>1Present address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.</mods:affiliation></affiliation></author><author><name sortKey="Butterworth, Byron E" sort="Butterworth, Byron E" uniqKey="Butterworth B" first="Byron E." last="Butterworth">Byron E. 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Male Fischer-344 rats were treated by gavage and hepatocytes were isolated by liver perfusion and cultured with [3H]thymidine. UDS was measured by quantitative autoradiography as net grains/nucleus (NG); ≥5 NG was considered positive. Controls consistently had − 3 to − 6 NG. A dose-related increase in UDS was observed 12 h after treatment, with 200 mg/kg tgDNT producing 26 NG. A 50-fold increase in the number of cells in S-phase was observed at 48 h after treatment. This increase in S-phase cells could be suppressed in the presence of 10–20 mM hydroxyurea (HU), while the same levels of HU did not affect the level of UDS at 12 h after treatment. 2, 4-DNT produced only a weak response, in contrast to 2, 6-DNT which was a potent inducer of UDS. Treatment of female rats with tgDNT yielded only modest increases in UDS and DNA replication relative to males. 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Male Fischer-344 rats were treated by gavage and hepatocytes were isolated by liver perfusion and cultured with [3H]thymidine. UDS was measured by quantitative autoradiography as net grains/nucleus (NG); ≥5 NG was considered positive. Controls consistently had − 3 to − 6 NG. A dose-related increase in UDS was observed 12 h after treatment, with 200 mg/kg tgDNT producing 26 NG. A 50-fold increase in the number of cells in S-phase was observed at 48 h after treatment. This increase in S-phase cells could be suppressed in the presence of 10–20 mM hydroxyurea (HU), while the same levels of HU did not affect the level of UDS at 12 h after treatment. 2, 4-DNT produced only a weak response, in contrast to 2, 6-DNT which was a potent inducer of UDS. Treatment of female rats with tgDNT yielded only modest increases in UDS and DNA replication relative to males. 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Mayo</json:string><json:string>Wayne Lab</json:string><json:string>B.E. BuHerworth</json:string><json:string>Dr Thomas</json:string><json:string>B.E. Butterworth</json:string><json:string>J. Popp</json:string><json:string>C. Mirsalis</json:string><json:string>Patricia Mullins</json:string><json:string>Smith</json:string><json:string>Marcus Hook</json:string><json:string>Stephen Dennis</json:string><json:string>Deborah Tove</json:string><json:string>IVa Induction</json:string><json:string>T. 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<front>
<journal-meta>
<journal-id journal-id-type="hwp">carcin</journal-id>
<journal-id journal-id-type="publisher-id">carcin</journal-id>
<journal-id journal-id-type="pmc">carcin</journal-id>
<journal-title>Carcinogenesis</journal-title>
<issn pub-type="epub">1460-2180</issn>
<issn pub-type="ppub">0143-3334</issn>
<publisher>
<publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1093/carcin/3.3.241</article-id>
<article-id pub-id-type="publisher-id">3.3.241</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Induction of unscheduled DNA synthesis in rat hepatocytes following <italic>in vivo</italic> treatment with dinitrotoluene</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Mirsalis</surname><given-names>Jon C.</given-names></name><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Butterworth</surname><given-names>Byron E.</given-names></name>
</contrib>
<aff><institution>Chemical Industry Institute of Toxicology</institution> <addr-line>Research Triangle Park, NC 27709, USA.</addr-line></aff>
</contrib-group>
<author-notes>
<corresp id="cor1"><sup>1</sup>Present address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<year>1982</year>
</pub-date>
<volume>3</volume>
<issue>3</issue>
<fpage>241</fpage>
<lpage>245</lpage>
<history>
<date date-type="received">
<day>03</day>
<month>8</month>
<year>1981</year>
</date>
<date date-type="rev-recd">
<day>19</day>
<month>10</month>
<year>1981</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>1</month>
<year>1982</year>
</date>
</history>
<copyright-statement>© 1982 IRL Press Limited</copyright-statement>
<copyright-year>1982</copyright-year>
<abstract>
<p>The purpose of this study was to examine the induction of unscheduled DNA synthesis (UDS) by the potent hepatocarcinogen technical grade dinitrotoluene (tgDNT; 76% 2, 4-DNT, 19% 2, 6-DNT) using the <italic>in vivo-in vitro</italic> hepatocyte DNA repair assay. Male Fischer-344 rats were treated by gavage and hepatocytes were isolated by liver perfusion and cultured with [<sup>3</sup>H]thymidine. UDS was measured by quantitative autoradiography as net grains/nucleus (NG); ≥5 NG was considered positive. Controls consistently had − 3 to − 6 NG. A dose-related increase in UDS was observed 12 h after treatment, with 200 mg/kg tgDNT producing 26 NG. A 50-fold increase in the number of cells in S-phase was observed at 48 h after treatment. This increase in S-phase cells could be suppressed in the presence of 10–20 mM hydroxyurea (HU), while the same levels of HU did not affect the level of UDS at 12 h after treatment. 2, 4-DNT produced only a weak response, in contrast to 2, 6-DNT which was a potent inducer of UDS. Treatment of female rats with tgDNT yielded only modest increases in UDS and DNA replication relative to males. These results are consistent with the carcinogenicity studies and indicate that tgDNT is a potent genotoxic agent, with 2, 6-DNT contributing the major portion of the effect.</p>
</abstract>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Induction of unscheduled DNA synthesis in rat hepatocytes following in vivo treatment with dinitrotoluene</title></titleInfo><name type="personal"><namePart type="given">Jon C.</namePart><namePart type="family">Mirsalis</namePart><affiliation>Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</affiliation><affiliation>1Present address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.</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, NC 27709, USA.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">1982</dateIssued><dateCreated encoding="w3cdtf">1982-01-10</dateCreated><copyrightDate encoding="w3cdtf">1982</copyrightDate></originInfo><abstract>The purpose of this study was to examine the induction of unscheduled DNA synthesis (UDS) by the potent hepatocarcinogen technical grade dinitrotoluene (tgDNT; 76% 2, 4-DNT, 19% 2, 6-DNT) using the in vivo-in vitro hepatocyte DNA repair assay. Male Fischer-344 rats were treated by gavage and hepatocytes were isolated by liver perfusion and cultured with [3H]thymidine. UDS was measured by quantitative autoradiography as net grains/nucleus (NG); ≥5 NG was considered positive. Controls consistently had − 3 to − 6 NG. A dose-related increase in UDS was observed 12 h after treatment, with 200 mg/kg tgDNT producing 26 NG. A 50-fold increase in the number of cells in S-phase was observed at 48 h after treatment. This increase in S-phase cells could be suppressed in the presence of 10–20 mM hydroxyurea (HU), while the same levels of HU did not affect the level of UDS at 12 h after treatment. 2, 4-DNT produced only a weak response, in contrast to 2, 6-DNT which was a potent inducer of UDS. Treatment of female rats with tgDNT yielded only modest increases in UDS and DNA replication relative to males. These results are consistent with the carcinogenicity studies and indicate that tgDNT is a potent genotoxic agent, with 2, 6-DNT contributing the major portion of the effect.</abstract><note type="author-notes">1Present address: SRI International, Building 205, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.</note><relatedItem type="host"><titleInfo><title>Carcinogenesis</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><topic>Articles</topic></subject><identifier type="ISSN">0143-3334</identifier><identifier type="eISSN">1460-2180</identifier><identifier type="PublisherID">carcin</identifier><identifier type="PublisherID-hwp">carcin</identifier><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>241</start><end>245</end></extent></part></relatedItem><identifier type="istex">91F2BDEFCDCDF672220F9D48EB2F24BE26DEA2E0</identifier><identifier type="ark">ark:/67375/HXZ-7X6PMMCT-Z</identifier><identifier type="DOI">10.1093/carcin/3.3.241</identifier><identifier type="ArticleID">3.3.241</identifier><accessCondition type="use and reproduction" contentType="copyright">© 1982 IRL Press Limited</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource><recordOrigin>Converted from (version 1.2.0) to MODS version 3.6.</recordOrigin><recordCreationDate encoding="w3cdtf">2019-12-09</recordCreationDate></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-7X6PMMCT-Z/record.json</uri></json:item></metadata><annexes><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-7X6PMMCT-Z/annexes.pdf</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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