{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:56:06Z","timestamp":1791194166716,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,14]],"date-time":"2006-07-14T00:00:00Z","timestamp":1152835200000},"content-version":"vor","delay-in-days":6403,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[1989,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A recent National Toxicology Program evaluation indicates that the rat hepatocyte\/DNA repair assay has a high false\u2010negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ\u2010specific carcinogens. In this study, we examined whether the sensitivity of the hepatocyte\/DNA repair assay might be increased through animal pretreatment with various hepatic mixed\u2010function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3\u2032,4,4\u2032\u2010tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measure of DNA damage and repair, were studied in cultures exposed to known and\/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4\u2032\u2010Oxydianiline, 1\u2010nitropy\u2010rene, and TCAB produced concentration\u2010dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4\u2032\u2010Oxydianiline and TCAB also induced a dose\u2010dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1\u2010nitropyrene was negative. 4,4\u2032\u2010Methylenedianiline produced a marginal response, and 3,3\u2032,4,4\u2032\u2010tetrachloroazoxybenzene (TCAOB) was negative in Aroclor\u2010 and pheno\u2010barbital\u2010induced hepatocytes; however, TCAOB, as well as TCAB, produced concentration\u2010dependent increases in UDS in TCAB\u2010induced hepatocytes. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte\/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed\u2010function oxidase inducers.<\/jats:p>","DOI":"10.1002\/em.2850130402","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T16:39:26Z","timestamp":1172075966000},"page":"281-288","source":"Crossref","is-referenced-by-count":22,"title":["Pretreatment with mixed\u2010function oxidase inducers increases the sensitivity of the hepatocyte\/DNA repair assay"],"prefix":"10.1002","volume":"13","author":[{"given":"J. G.","family":"Shaddock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. H.","family":"Heflich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. C.","family":"McMillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Hinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. A.","family":"Casciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,14]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.8.2281"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(88)90114-0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bk-1985-0283.ch015"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(86)90053-6"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(84)90166-6"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(87)90017-6"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(78)80035-4"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(83)90146-X"},{"key":"e_1_2_1_10_1","first-page":"49","article-title":"An evaluation of 27 coded chemicals using the primary hepatocyte\/DNA repair system","volume":"6","author":"Casciano DA","year":"1984","journal-title":"Environ Mutagen"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(79)90195-7"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/7.7.1073"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/5.11.1449"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(84)90028-9"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01056933"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860070313"},{"key":"e_1_2_1_17_1","first-page":"1158","article-title":"Induction of rat mammary gland tumors by 1\u2010nitropyrene, a recently recognized environmental mutagen","volume":"44","author":"Hirose M","year":"1984","journal-title":"Cancer Res"},{"key":"e_1_2_1_18_1","first-page":"225","article-title":"3,4,3\u2032,4\u2032\u2010tetrachloroazobenzene: A potential environmental toxicant","volume":"17","author":"Hsia MTS","year":"1977","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_1_19_1","first-page":"319","article-title":"Induction of hepatic microsomal cytochrome P\u2010448 by 3,3\u2032,4,4\u2032\u2010tetrachloroazobenzene and the corresponding azoxy and hydrazo analogs","volume":"25","author":"Hsia MTS","year":"1979","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(79)80035-X"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860070607"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00058453"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860060407"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(83)90190-2"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(83)90026-5"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2797(81)90084-3"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90107-8"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(87)90049-2"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(82)90068-4"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2797(80)90149-0"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00919786"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/7.1.89"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.22.040182.002505"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860030103"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(83)90034-9"},{"key":"e_1_2_1_36_1","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/S0021-9258(17)34211-4","article-title":"Separation and characterization of highly purified forms of liver microsomal cytochrome P\u2010450 from rats treated with polychlorinated biphenyls, phenobarbital and 3\u2010methylcholanthrene","volume":"254","author":"Ryan DE","year":"1979","journal-title":"J Biol Chem"},{"key":"e_1_2_1_37_1","first-page":"521","article-title":"Properties of purified liver microsomal cytochrome P\u2010450 from rats treated with the polychlorinated biphenyl mixture Aroclor 1254","volume":"13","author":"Ryan DE","year":"1977","journal-title":"Mol Pharmacol"},{"key":"e_1_2_1_38_1","first-page":"3169","article-title":"Participation of cytochrome P\u2010450 in reductive metabolism of 1\u2010nitropyrene by rat microsomes","volume":"44","author":"Saito K","year":"1984","journal-title":"Cancer Res"},{"key":"e_1_2_1_39_1","first-page":"527","article-title":"Hepatocellular pathotoxicology of 3,3\u2032,4,4\u2032\u2010tetrachloroazobenzene and 3,3\u2032,4,4\u2032\u2010tetrachloroazoxybenzene in the rodent. I. In vivo studies","volume":"28","author":"Schrankel KR","year":"1980","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_1_40_1","unstructured":"SpaldingJW ShaddockJG MirsalisJC CascianoDA(1988):Evaluation of 45 rodent carcinogens and non\u2010carcinogens in the in vitro rat hepatocyte DNA repair assay. Environ Molec Mutagen (Submitted)."},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3554512"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860030408"},{"key":"e_1_2_1_43_1","first-page":"221","article-title":"Carcinogen\u2010induced DNA repair in primary rat liver cell cultures: A possible screen for chemical carcinogens","volume":"1","author":"Williams GM","year":"1976","journal-title":"Cancer Lett"},{"key":"e_1_2_1_44_1","first-page":"1845","article-title":"The detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures","volume":"37","author":"Williams GM","year":"1977","journal-title":"Cancer Res"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(78)93522-X"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(79)80034-8"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(82)90003-6"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(80)90141-X"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fem.2850130402","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.2850130402","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T18:30:12Z","timestamp":1695753012000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.2850130402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,1]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1989,1]]}},"alternative-id":["10.1002\/em.2850130402"],"URL":"https:\/\/doi.org\/10.1002\/em.2850130402","archive":["Portico"],"relation":{},"ISSN":["0893-6692","1098-2280"],"issn-type":[{"value":"0893-6692","type":"print"},{"value":"1098-2280","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,1]]}}}