title: o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in mouse liver.
abstract: The objective of this study was to investigate the CYP1A1 and CYP1A2 mRNAs and enzyme activities in mouse liver during induction with o-aminoazotoluene (OAT) as well as the capability of the hepatic S9-fraction from OAT-treated mice to induce its own activation to mutagens in the Ames test using S. typhymurium strain TA98. The data obtained indicate that when used at appropriate doses, OAT is a PAH-type inducer of mouse hepatic microsomal monooxygenases, which activity is not less than that of the known inducer 3,4-benzo[alpha]pyrene. In the absence of S9-fraction enzymes no OAT-mediated mutagenicity was observed in the Ames test. In the presence of the S9-fraction from OAT-pretreated mice, OAT induced as high revertant numbers, as it did in the presence of the S9 fraction from the liver of Aroclor 1254-treated mice. Thus, OAT does induce the enzymes of its own mutagenic activation in mouse liver.
authors.affiliation: Laboratory of Molecular Mechanisms of Carcinogenesis, Institute of Molecular Biology and Biophysics, Timakov Street 2, Novosibirsk 630117, Russia. pharmacogenomics@ngs.ru
authors.forename: Olga N
authors.initials: ON
authors.lastname: Mikhailova
authors.forename: Elena A
authors.initials: EA
authors.lastname: Vasyunina
authors.forename: Ludmila P
authors.initials: LP
authors.lastname: Ovchinnikova
authors.forename: Lyudmila F
authors.initials: LF
authors.lastname: Gulyaeva
authors.forename: Olga A
authors.initials: OA
authors.lastname: Timofeeva
authors.forename: Maxim L
authors.initials: ML
authors.lastname: Filipenko
authors.forename: Vasily I
authors.initials: VI
authors.lastname: Kaledin
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D004790:Enzyme Induction / Q000187:drug effects*; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D009762:o-Aminoazotoluene / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018076:DNA, Complementary; D009153:Mutagens; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; D012313:RNA; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D009762:o-Aminoazotoluene