Elevation of hepatic microsomal epoxide hydrolase activity by 2-acetylaminofluorene: strain and species differences
Identifieur interne : 000710 ( Istex/Corpus ); précédent : 000709; suivant : 000711Elevation of hepatic microsomal epoxide hydrolase activity by 2-acetylaminofluorene: strain and species differences
Auteurs : M. Elizabeth Graichen ; John G. DentSource :
- Carcinogenesis [ 0143-3334 ] ; 1984.
Abstract
Hepatocarcinogens have been shown to cause marked elevation of hepatic microsomal epoxide hydrobase activity in the rat at short intervals after administration. The present studies were designed to characterize 2-acetylaminofluorene (AAF) mediated epoxide hydrolase elevation and to investigate the relationship between epoxide hydrolase increases, AAF metabolism, and hepatocarcinogenicity. Oral or i.p. administration of AAF to F-344 rats produced log-linear doseresponse curves for epoxide hydrolase elevation, measured with either benzo[a]pyrene-4, 5-oxide or styrene oxide substrate. Following a single dose of AAF (35 mg/kg), epoxide hydrolase activity was maximally increased (560% of control) within 48 h, and the activity declined slowly, with a halflife of 17.5 days. Co-treatment with actinomycin D effectively blocked the AAF dependent increase in epoxide hydrolase, suggesblng that de novo protein synthesis is associated with the increase in enzyme activity. Dose-response curves for epoxide hydrolase induction by AAF, N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and aminofluorene were compared, and the potencies for increasing epoxide hydrolase activity reflected the relative hepatocarcinogenic potentials of these agents. In mice, which are resistant to the hepatocarcinogenic action of AAF and deficient in AAF-N-hydroxylase activity, AAF caused no significant increase in hepatic microsomal epoxide hydrolase activity. Similarly, in Cotton rats and guinea pigs, which are lacking in ability to form the sulfate conjugate of N-OH-AAF, neither i.p. nor dietary administration of AAF elicited increases in epoxide hydrolase activity at doses which were maximally effective in F-344 rats. These results support the hypothesis that the ability of compounds to increase epoxide hydrolase activity is related to their carcinogenic potency. Furthermore, the results suggest that increases in epoxide hydrolase activity are associated with metabolism of AAF to the putative proximate carcinogen N-OH-AAF, and the subsequent conversion of this compound to the N-O-sulfate conjugate.
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DOI: 10.1093/carcin/5.1.23
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Elizabeth" last="Graichen">M. Elizabeth Graichen</name><affiliation><mods:affiliation>Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</mods:affiliation></affiliation><affiliation><mods:affiliation></mods:affiliation></affiliation></author><author><name sortKey="Dent, John G" sort="Dent, John G" uniqKey="Dent J" first="John G." last="Dent">John G. Dent</name><affiliation><mods:affiliation>Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</mods:affiliation></affiliation><affiliation><mods:affiliation>2To whom reprint requests should be sent</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Carcinogenesis</title><idno type="eISSN">1460-2180</idno><idno type="ISSN">0143-3334</idno><imprint><publisher>Oxford University Press</publisher><date when="1984-01">1984</date><biblScope unit="vol">5</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="23">23</biblScope><biblScope unit="page" to="28">28</biblScope></imprint><idno type="ISSN">0143-3334</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0143-3334</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Hepatocarcinogens have been shown to cause marked elevation of hepatic microsomal epoxide hydrobase activity in the rat at short intervals after administration. The present studies were designed to characterize 2-acetylaminofluorene (AAF) mediated epoxide hydrolase elevation and to investigate the relationship between epoxide hydrolase increases, AAF metabolism, and hepatocarcinogenicity. Oral or i.p. administration of AAF to F-344 rats produced log-linear doseresponse curves for epoxide hydrolase elevation, measured with either benzo[a]pyrene-4, 5-oxide or styrene oxide substrate. Following a single dose of AAF (35 mg/kg), epoxide hydrolase activity was maximally increased (560% of control) within 48 h, and the activity declined slowly, with a halflife of 17.5 days. Co-treatment with actinomycin D effectively blocked the AAF dependent increase in epoxide hydrolase, suggesblng that de novo protein synthesis is associated with the increase in enzyme activity. Dose-response curves for epoxide hydrolase induction by AAF, N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and aminofluorene were compared, and the potencies for increasing epoxide hydrolase activity reflected the relative hepatocarcinogenic potentials of these agents. In mice, which are resistant to the hepatocarcinogenic action of AAF and deficient in AAF-N-hydroxylase activity, AAF caused no significant increase in hepatic microsomal epoxide hydrolase activity. Similarly, in Cotton rats and guinea pigs, which are lacking in ability to form the sulfate conjugate of N-OH-AAF, neither i.p. nor dietary administration of AAF elicited increases in epoxide hydrolase activity at doses which were maximally effective in F-344 rats. These results support the hypothesis that the ability of compounds to increase epoxide hydrolase activity is related to their carcinogenic potency. 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Elizabeth</forename></persName><affiliation><orgName type="department">Department of Biochemical Toxicology</orgName><orgName type="institution">Chemical Industry Institute of Toxicology</orgName><address><addrLine>Research Triangle Park, NC 27709, USA.</addrLine></address></affiliation><note place="foot" n="fn1"><p><hi rend="superscript">1</hi>Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</p></note></author><author xml:id="author-0001"><persName><surname>Dent</surname><forename type="first">John G.</forename></persName><affiliation><orgName type="department">Department of Biochemical Toxicology</orgName><orgName type="institution">Chemical Industry Institute of Toxicology</orgName><address><addrLine>Research Triangle Park, NC 27709, USA.</addrLine></address></affiliation><note place="foot" n="fn1"><p><hi rend="superscript">1</hi>Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</p></note><affiliation role="corresp">2To whom reprint requests should be sent</affiliation></author><idno type="istex">C4D7642A7EC54BEC6FCFD43D17C98FA7B55C0C8C</idno><idno type="ark">ark:/67375/HXZ-QHK1WPD9-J</idno><idno type="DOI">10.1093/carcin/5.1.23</idno><idno type="publisher-id">5.1.23</idno></analytic><monogr><title level="j" type="main">Carcinogenesis</title><idno type="hwp">carcin</idno><idno type="publisher-id">carcin</idno><idno type="pmc">carcin</idno><idno type="eISSN">1460-2180</idno><idno type="pISSN">0143-3334</idno><imprint><publisher>Oxford University Press</publisher><date when="1984-01">1984</date><biblScope unit="vol">5</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="23">23</biblScope><biblScope unit="page" to="28">28</biblScope></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="2019-12-09"><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.
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<front>
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<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>
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<article-id pub-id-type="doi">10.1093/carcin/5.1.23</article-id>
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<subject>ORIGINAL ARTICLES</subject>
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<title-group>
<article-title>Elevation of hepatic microsomal epoxide hydrolase activity by 2-acetylaminofluorene: strain and species differences</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Graichen</surname><given-names>M. Elizabeth</given-names></name><xref ref-type="fn" rid="fn1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Dent</surname><given-names>John G.</given-names></name><xref ref-type="fn" rid="fn1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref>
</contrib>
<aff><institution>Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology</institution> <addr-line>Research Triangle Park, NC 27709, USA.</addr-line></aff>
</contrib-group>
<author-notes>
<fn id="fn1"><p><sup>1</sup>Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</p></fn>
<corresp id="cor1"><sup>2</sup>To whom reprint requests should be sent</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>1</month>
<year>1984</year>
</pub-date>
<volume>5</volume>
<issue>1</issue>
<fpage>23</fpage>
<lpage>28</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>6</month>
<year>1983</year>
</date>
<date date-type="accepted">
<day>01</day>
<month>10</month>
<year>1983</year>
</date>
</history>
<copyright-statement>© IRL Press Ltd.</copyright-statement>
<copyright-year>1984</copyright-year>
<abstract>
<p>Hepatocarcinogens have been shown to cause marked elevation of hepatic microsomal epoxide hydrobase activity in the rat at short intervals after administration. The present studies were designed to characterize 2-acetylaminofluorene (AAF) mediated epoxide hydrolase elevation and to investigate the relationship between epoxide hydrolase increases, AAF metabolism, and hepatocarcinogenicity. Oral or i.p. administration of AAF to F-344 rats produced log-linear doseresponse curves for epoxide hydrolase elevation, measured with either benzo[a]pyrene-4, 5-oxide or styrene oxide substrate. Following a single dose of AAF (35 mg/kg), epoxide hydrolase activity was maximally increased (560% of control) within 48 h, and the activity declined slowly, with a halflife of 17.5 days. Co-treatment with actinomycin D effectively blocked the AAF dependent increase in epoxide hydrolase, suggesblng that de novo protein synthesis is associated with the increase in enzyme activity. Dose-response curves for epoxide hydrolase induction by AAF, N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and aminofluorene were compared, and the potencies for increasing epoxide hydrolase activity reflected the relative hepatocarcinogenic potentials of these agents. In mice, which are resistant to the hepatocarcinogenic action of AAF and deficient in AAF-N-hydroxylase activity, AAF caused no significant increase in hepatic microsomal epoxide hydrolase activity. Similarly, in Cotton rats and guinea pigs, which are lacking in ability to form the sulfate conjugate of N-OH-AAF, neither i.p. nor dietary administration of AAF elicited increases in epoxide hydrolase activity at doses which were maximally effective in F-344 rats. These results support the hypothesis that the ability of compounds to increase epoxide hydrolase activity is related to their carcinogenic potency. Furthermore, the results suggest that increases in epoxide hydrolase activity are associated with metabolism of AAF to the putative proximate carcinogen N-OH-AAF, and the subsequent conversion of this compound to the N-O-sulfate conjugate.</p>
</abstract>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Elevation of hepatic microsomal epoxide hydrolase activity by 2-acetylaminofluorene: strain and species differences</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Elevation of hepatic microsomal epoxide hydrolase activity by 2-acetylaminofluorene: strain and species differences</title></titleInfo><name type="personal"><namePart type="given">M. Elizabeth</namePart><namePart type="family">Graichen</namePart><affiliation>Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</affiliation><affiliation></affiliation><description>1Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John G.</namePart><namePart type="family">Dent</namePart><affiliation>Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.</affiliation><affiliation>2To whom reprint requests should be sent</affiliation><description>1Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</description><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">1984-01</dateIssued><dateCreated encoding="w3cdtf">1983-10-01</dateCreated><copyrightDate encoding="w3cdtf">1984</copyrightDate></originInfo><abstract>Hepatocarcinogens have been shown to cause marked elevation of hepatic microsomal epoxide hydrobase activity in the rat at short intervals after administration. The present studies were designed to characterize 2-acetylaminofluorene (AAF) mediated epoxide hydrolase elevation and to investigate the relationship between epoxide hydrolase increases, AAF metabolism, and hepatocarcinogenicity. Oral or i.p. administration of AAF to F-344 rats produced log-linear doseresponse curves for epoxide hydrolase elevation, measured with either benzo[a]pyrene-4, 5-oxide or styrene oxide substrate. Following a single dose of AAF (35 mg/kg), epoxide hydrolase activity was maximally increased (560% of control) within 48 h, and the activity declined slowly, with a halflife of 17.5 days. Co-treatment with actinomycin D effectively blocked the AAF dependent increase in epoxide hydrolase, suggesblng that de novo protein synthesis is associated with the increase in enzyme activity. Dose-response curves for epoxide hydrolase induction by AAF, N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and aminofluorene were compared, and the potencies for increasing epoxide hydrolase activity reflected the relative hepatocarcinogenic potentials of these agents. In mice, which are resistant to the hepatocarcinogenic action of AAF and deficient in AAF-N-hydroxylase activity, AAF caused no significant increase in hepatic microsomal epoxide hydrolase activity. Similarly, in Cotton rats and guinea pigs, which are lacking in ability to form the sulfate conjugate of N-OH-AAF, neither i.p. nor dietary administration of AAF elicited increases in epoxide hydrolase activity at doses which were maximally effective in F-344 rats. These results support the hypothesis that the ability of compounds to increase epoxide hydrolase activity is related to their carcinogenic potency. Furthermore, the results suggest that increases in epoxide hydrolase activity are associated with metabolism of AAF to the putative proximate carcinogen N-OH-AAF, and the subsequent conversion of this compound to the N-O-sulfate conjugate.</abstract><note type="footnotes">1Present address: Department of Drug Metabolism, Smith Kline & French Laboratories PO Box 7929, Philadelphia, PA 19101, USA.</note><note type="author-notes">2To whom reprint requests should be sent</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>ORIGINAL 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>1984</date><detail type="volume"><caption>vol.</caption><number>5</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>23</start><end>28</end></extent></part></relatedItem><identifier type="istex">C4D7642A7EC54BEC6FCFD43D17C98FA7B55C0C8C</identifier><identifier type="ark">ark:/67375/HXZ-QHK1WPD9-J</identifier><identifier type="DOI">10.1093/carcin/5.1.23</identifier><identifier type="ArticleID">5.1.23</identifier><accessCondition type="use and reproduction" contentType="copyright">© IRL Press Ltd.</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-QHK1WPD9-J/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-QHK1WPD9-J/annexes.pdf</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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