o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in mouse liver.
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.
Mikhailova
Olga N
ON
Laboratory of Molecular Mechanisms of Carcinogenesis, Institute of Molecular Biology and Biophysics, Timakov Street 2, Novosibirsk 630117, Russia. pharmacogenomics@ngs.ru
Vasyunina
Elena A
EA
Ovchinnikova
Ludmila P
LP
Gulyaeva
Lyudmila F
LF
Timofeeva
Olga A
OA
Filipenko
Maxim L
ML
Kaledin
Vasily I
VI
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
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