{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:13:11Z","timestamp":1790903591634,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"3","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>The in vivo\u2010in vitro hepatocyte DNA repair assay has been shown to be useful for studying genotoxic hepatocarcinogens. In addition, measurement of S\u2010phase synthesis (SPS) provides an indirect indicator of hepatocellular proliferation, which may be an important mechanism in rodent carcinogenesis. This assay was used to examine 24 chemicals for their ability to induce unscheduled DNA synthesis (UDS) or SPS in Fischer\u2010344 rats or B6C3F1 mice following in vivo treatment. Hepatocytes were isolated by liver perfusion and incubated with <jats:sup>3<\/jats:sup>H\u2010thymidine following in vivo treatment by gavage. UDS was measured by quantitative autoradiography as net grains\/ nucleus (NG). Controls from both sexes of both species yielded &lt;0.0 NG. Chemicals chosen for testing were from the National Toxicology Program (NTP) genetic toxicology testing program and most were also evaluated in long\u2010term animal studies conducted by the NTP. 11\u2010Aminoun\u2010decanoic acid, benzyl acetate, bis(2\u2010chloro\u20101\u2010methylethyl)ether (BCMEE), C.I. Solvent Yellow 14, cinnamaldehyde, cinnamyl anthranilate, dichloromethane, dichlorvos, glutaraldehyde, 4,4\u2032\u2010methylenedianiline (MDA), 4\u2010nitrotoluene, 4,4\u2032\u2010oxydianiline, a polybrominated biphenyl mixture (PBB), reserpine, 1,1,2,2\u2010tetrachloroethane, 1,1,2\u2010trichloroethane, trichloroethylene, and 2,6\u2010xylidine all failed to induce UDS in rats and\/or mice. Dinitrotoluene and Michler's Ketone induced positive UDS response in rat, while N\u2010nitrosodiethanolamine and selenium sulfide induced equivocal UDS results in mouse and rat, respectively. BCMEE, bromoform, chloroform, PBB, 1,1,2\u2010trichloroethane, and trichloroethylene were all potent inducers of SPS in mouse liver, while C.I. Solvent Yellow 14, and 1,1,2,2\u2010tetrachloroethane yielded equivocal SPS results in rat and mouse, respectively. These results indicate that most of the test compounds do not induce UDS in the liver; however, the significant S\u2010phase response induced by many of these compounds, especially the halogenated solvents, may be an important mechanism in their hepatocarcinogenicity.<\/jats:p>","DOI":"10.1002\/em.2850140305","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T16:38:01Z","timestamp":1172075881000},"page":"155-164","source":"Crossref","is-referenced-by-count":157,"title":["Measurement of unscheduled DNA synthesis and S\u2010phase synthesis in rodent hepatocytes following in vivo treatment: Testing of 24 compounds"],"prefix":"10.1002","volume":"14","author":[{"given":"Jon C.","family":"Mirsalis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Kim","family":"Tyson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica K.","family":"Loh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol M.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Bakke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judson W.","family":"Spalding","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":"10.1016\/0165-1218(88)90114-0"},{"key":"e_1_2_1_3_1","unstructured":"Canadian Minister of National Health and Welfare(1986):Guidelines on the use of mutagenicity tests in the toxicological evaluation of chemicals. Ottawa Canada pp61\u201364"},{"key":"e_1_2_1_4_1","unstructured":"Chemical Industry Institute of Toxicology(1978):A twenty\u2010four month toxicology study in Fischer\u2010344 rats given dinitrotoluene 12 month report Docket No. 327N8"},{"key":"e_1_2_1_5_1","first-page":"2836","article-title":"Influence of intestinal bacteria, sex of the animal, and position of the nitro group on the hepatic genotoxicity of nitrotoluene isomers in vivo","volume":"43","author":"Doolittle DJ","year":"1983","journal-title":"Cancer Res"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(87)90066-8"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860050703"},{"key":"e_1_2_1_8_1","first-page":"401","volume":"20","author":"International Agency for Research on Cancer","year":"1979","journal-title":"IARC Monogr Eval Carcinog Risk Chem Hum"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860070106"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/6.12.1679"},{"key":"e_1_2_1_11_1","first-page":"119","volume-title":"Banbury Report 25: Nongenotoxic Mechanisms of Carcinogenesis","author":"Loury DJ","year":"1987"},{"key":"e_1_2_1_12_1","first-page":"87","article-title":"Contrasting effects of di(2\u2010ethylhexyl)phthalate and WY\u201014,643 on hepatocyte proliferation and carcinogenicity in male F344 rats","volume":"29","author":"Marsman DS","year":"1988","journal-title":"Proc Am Assoc Cancer Res"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00058454"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/3.3.241"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860040506"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/6.10.1521"},{"issue":"11","key":"e_1_2_1_17_1","first-page":"71","article-title":"Evaluation of the potential of riddelline to induce unscheduled DNA synthesis, S\u2010phase synthesis or micronuclei following in vivo treatment with multiple doses","volume":"11","author":"Mirsalis JC","year":"1988","journal-title":"Environ Mutagen"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-4664-7_8"},{"issue":"11","key":"e_1_2_1_19_1","first-page":"93","article-title":"Pretreatment with mixed\u2010function oxidase enzyme inducers increases the sensitivity of the hepatocyte\/DNA repair assay","volume":"11","author":"Shaddock JG","year":"1988","journal-title":"Environ Mutagen"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/9.6.959"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.2307\/3430581"},{"key":"e_1_2_1_22_1","first-page":"1845","article-title":"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"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fem.2850140305","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.2850140305","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T12:47:17Z","timestamp":1697978837000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.2850140305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,1]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1989,1]]}},"alternative-id":["10.1002\/em.2850140305"],"URL":"https:\/\/doi.org\/10.1002\/em.2850140305","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]]}}}