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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzo(a)pyrene / metabolism
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Biotransformation / drug effects
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Chlorodiphenyl (54% Chlorine) / pharmacology
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Cytochrome P-450 CYP1A1 / biosynthesis
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Cytochrome P-450 CYP1A2 / biosynthesis
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DNA, Complementary / biosynthesis
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DNA, Complementary / isolation & purification
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Enzyme Induction / drug effects*
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Hydroxylation
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Liver / drug effects
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Liver / enzymology*
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Male
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Mice
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Mice, Inbred C57BL
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Mutagenicity Tests
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Mutagens / metabolism*
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Mutagens / toxicity*
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RNA / biosynthesis
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RNA / isolation & purification
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Reverse Transcriptase Polymerase Chain Reaction
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Subcellular Fractions / drug effects
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Subcellular Fractions / enzymology
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o-Aminoazotoluene / metabolism
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o-Aminoazotoluene / pharmacology*
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o-Aminoazotoluene / toxicity
Substances
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DNA, Complementary
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Mutagens
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Chlorodiphenyl (54% Chlorine)
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Benzo(a)pyrene
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RNA
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP1A2
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o-Aminoazotoluene