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After 13\u2010wk treatment, glutathione <jats:italic>S<\/jats:italic>\u2010transferase placental form (GST\u2010P)\u2010positive liver cell foci were significantly increased in NPYR\u2010treated and IQ\u2010treated rats. In the DEHP\u2010treated rats, marked hepatomegaly with centrilobular hypertrophy of hepatocytes occurred, although GST\u2010P staining was consistently negative. Positive mutagenicity was detected in IQ\u2010 and NPYR\u2010treated rats. Mutant frequencies (MFs) in the liver DNA were 188.0\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> and 56.5\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>, approximately 35\u2010fold and 10\u2010fold higher, respectively, than that of nontreatment control rats (5.5\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). There were no increases in MFs in the DEHP\u2010 or AAP\u2010treated rats as compared to the nontreatment control value. IQ induced mainly base substitutions leading to G:C to T:A transversions (56.9%) and deletions of G:C base pairs. In contrast, NPYR primarily caused specific A:T to G:C transitions (49.3%), which are very rare in the other groups. These data provided support for the conclusion that IQ and NPYR hepatocarcinogenesis depends on genotoxic processes and specific DNA adduct formation while DEHP exerts its influence via a nongenotoxic promotional pathway. Our data also indicate that analysis of specific in vivo mutational responses with transgenic animal models can provide crucial information for understanding the molecular mechanisms underlying chemical carcinogenesis. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20061","type":"journal-article","created":{"date-parts":[[2004,10,15]],"date-time":"2004-10-15T07:03:33Z","timestamp":1097823813000},"page":"9-17","source":"Crossref","is-referenced-by-count":49,"title":["In vivo mutational analysis of liver DNA in <i>gpt<\/i> delta transgenic rats treated with the hepatocarcinogens <i>N<\/i>\u2010nitrosopyrrolidine, 2\u2010amino\u20103\u2010methylimidazo[4,5\u2010<i>f<\/i>]quinoline, and di(2\u2010ethylhexyl)phthalate"],"prefix":"10.1002","volume":"42","author":[{"given":"Keita","family":"Kanki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyoshi","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken\u2010ichi","family":"Masumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Umemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Imazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuki","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiko","family":"Nohmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,15]]},"reference":[{"key":"e_1_2_7_2_2","first-page":"107","article-title":"Carcinogenicity and mutagenicity of N\u2010nitroso compounds","volume":"1","author":"Lijinsky W","year":"1987","journal-title":"Mol Toxicol"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940040604"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(91)90106-V"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(99)00100-X"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(00)00077-4"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.10152"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2280(1996)28:4<465::AID-EM24>3.0.CO;2-C"},{"key":"e_1_2_7_9_2","first-page":"1988","article-title":"The effect of substituents on the carcinogenicity of N\u2010nitrosopyrrolidine in Sprague\u2010Dawley Rats","volume":"36","author":"Lijinsky W","year":"1976","journal-title":"Cancer Res"},{"key":"e_1_2_7_10_2","first-page":"313","article-title":"Evaluation of the carcinogenic risk of chemicals to humans: Some N\u2010nitroso compounds","volume":"39","author":"Bartsch H","year":"1978","journal-title":"IARC Sci Publ"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx010097i"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(87)90026-1"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940030304"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/15.6.473"},{"key":"e_1_2_7_15_2","unstructured":"IARC.IQ (2\u2010amino\u20103\u2010methylimidazo[4 5\u2010f]quinoline). 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