Evaluation of positive controls for the in vitro unscheduled DNA synthesis assay using hepatocytes from induced (Aroclor 1254) and uninduced male cynomolgus monkey

We have evaluated the use of four different positive control compounds for assessing UDS in monkey hepatocytes and have found three of these, methylmethanesulfonate, benzo[a]pyrene, and dimethylbenz[a]anthracene, to produce strong positive responses in vitro. Dimethylnitrosamine induced only weak re...

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Veröffentlicht in:Environmental and molecular mutagenesis 1997, Vol.30 (3), p.354-358
Hauptverfasser: Hamilton, Carol M., Dabbs, Jack E., Cunningham, Glenn D., Vernetti, Lawrence A., Mirsalis, Jon C., Snyder, Ronald D.
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container_end_page 358
container_issue 3
container_start_page 354
container_title Environmental and molecular mutagenesis
container_volume 30
creator Hamilton, Carol M.
Dabbs, Jack E.
Cunningham, Glenn D.
Vernetti, Lawrence A.
Mirsalis, Jon C.
Snyder, Ronald D.
description We have evaluated the use of four different positive control compounds for assessing UDS in monkey hepatocytes and have found three of these, methylmethanesulfonate, benzo[a]pyrene, and dimethylbenz[a]anthracene, to produce strong positive responses in vitro. Dimethylnitrosamine induced only weak responses. We also report that the strength of the response induced by procarcinogens was not enhanced in hepatocytes taken from Aroclor 1254‐pretreated monkeys, even though substantial induction of cytochrome P450 enzymes was demonstrated in these cells. These studies raise the question of the utility of employing an in vivo induction system to enhance the monkey UDS assay. Environ. Mol. Mutagen. 30:354–358, 1997 © 1997 Wiley‐Liss, Inc.
doi_str_mv 10.1002/(SICI)1098-2280(1997)30:3<354::AID-EM15>3.0.CO;2-C
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Mol. Mutagen</addtitle><description>We have evaluated the use of four different positive control compounds for assessing UDS in monkey hepatocytes and have found three of these, methylmethanesulfonate, benzo[a]pyrene, and dimethylbenz[a]anthracene, to produce strong positive responses in vitro. Dimethylnitrosamine induced only weak responses. We also report that the strength of the response induced by procarcinogens was not enhanced in hepatocytes taken from Aroclor 1254‐pretreated monkeys, even though substantial induction of cytochrome P450 enzymes was demonstrated in these cells. These studies raise the question of the utility of employing an in vivo induction system to enhance the monkey UDS assay. Environ. Mol. 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Dabbs, Jack E. ; Cunningham, Glenn D. ; Vernetti, Lawrence A. ; Mirsalis, Jon C. ; Snyder, Ronald D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3865-849144bb57bd35e9c70b5f1d8c890e4e9a0f65a5ae0c0423df55f42973b2f9f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>12-dimethylbenz[a]anthracene</topic><topic>7,12‐dimethylbenz[a]anthracene</topic><topic>9,10-Dimethyl-1,2-benzanthracene - toxicity</topic><topic>Animals</topic><topic>Aroclor 1254</topic><topic>Aroclors - pharmacology</topic><topic>Benzo(a)pyrene - toxicity</topic><topic>benzo[a]pyrene</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Chemical mutagenesis</topic><topic>dimethylnitrosamine</topic><topic>Dimethylnitrosamine - toxicity</topic><topic>DNA Repair</topic><topic>Enzyme Induction</topic><topic>hepatocytes</topic><topic>in vitro</topic><topic>Liver</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methyl Methanesulfonate - toxicity</topic><topic>methylmethanesulfonate</topic><topic>monkeys</topic><topic>Mutagenicity Tests - methods</topic><topic>Toxicology</topic><topic>UDS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamilton, Carol M.</creatorcontrib><creatorcontrib>Dabbs, Jack E.</creatorcontrib><creatorcontrib>Cunningham, Glenn D.</creatorcontrib><creatorcontrib>Vernetti, Lawrence A.</creatorcontrib><creatorcontrib>Mirsalis, Jon C.</creatorcontrib><creatorcontrib>Snyder, Ronald D.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Environmental and molecular mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamilton, Carol M.</au><au>Dabbs, Jack E.</au><au>Cunningham, Glenn D.</au><au>Vernetti, Lawrence A.</au><au>Mirsalis, Jon C.</au><au>Snyder, Ronald D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of positive controls for the in vitro unscheduled DNA synthesis assay using hepatocytes from induced (Aroclor 1254) and uninduced male cynomolgus monkey</atitle><jtitle>Environmental and molecular mutagenesis</jtitle><addtitle>Environ. Mol. Mutagen</addtitle><date>1997</date><risdate>1997</risdate><volume>30</volume><issue>3</issue><spage>354</spage><epage>358</epage><pages>354-358</pages><issn>0893-6692</issn><eissn>1098-2280</eissn><coden>EMMUEG</coden><abstract>We have evaluated the use of four different positive control compounds for assessing UDS in monkey hepatocytes and have found three of these, methylmethanesulfonate, benzo[a]pyrene, and dimethylbenz[a]anthracene, to produce strong positive responses in vitro. Dimethylnitrosamine induced only weak responses. We also report that the strength of the response induced by procarcinogens was not enhanced in hepatocytes taken from Aroclor 1254‐pretreated monkeys, even though substantial induction of cytochrome P450 enzymes was demonstrated in these cells. These studies raise the question of the utility of employing an in vivo induction system to enhance the monkey UDS assay. Environ. Mol. 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subjects 12-dimethylbenz[a]anthracene
7,12‐dimethylbenz[a]anthracene
9,10-Dimethyl-1,2-benzanthracene - toxicity
Animals
Aroclor 1254
Aroclors - pharmacology
Benzo(a)pyrene - toxicity
benzo[a]pyrene
Biological and medical sciences
Biotransformation
Chemical mutagenesis
dimethylnitrosamine
Dimethylnitrosamine - toxicity
DNA Repair
Enzyme Induction
hepatocytes
in vitro
Liver
Macaca fascicularis
Male
Medical sciences
Methyl Methanesulfonate - toxicity
methylmethanesulfonate
monkeys
Mutagenicity Tests - methods
Toxicology
UDS
title Evaluation of positive controls for the in vitro unscheduled DNA synthesis assay using hepatocytes from induced (Aroclor 1254) and uninduced male cynomolgus monkey
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