Cytosolic activation of 2-aminoanthracene: implications in its use as diagnostic mutagen in the Ames test.
The metabolic activation of 2-aminoanthracene to mutagens in the Ames test was investigated using hepatic S9, microsomal and cytosolic fractions from control and Aroclor 1254-treated rats as activation systems. Microsomal and S9 preparations from control animals could activate 2-aminoanthracene, but the efficiency of activation was suppressed by pretreatment of animals with Aroclor 1254. Cytosolic fractions from Aroclor 1254-treated rats could readily activate the promutagen more readily than microsomes. The cytosolic activation of 2-aminoanthracene required NADPH and could not be accounted for by possible microsomal contamination. The molybdenum oxygenases appear not to contribute to the cytosolic activation of this promutagen. It is concluded that (a) the microsomal activation of 2-aminoanthracene is catalysed more effectively by enzyme systems other than the P450 I family and (b) an enzyme system capable of activating this carcinogen in vitro is present in the hepatic cytosol. The implications of these findings in the use of 2-aminoanthracene as a positive control in the Ames test are discussed.
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, Great Britain.
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Ayrton
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Neville
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Ioannides
D000818:Animals; D000873:Anthracenes / Q000493:pharmacokinetics*; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D020111:Chlorodiphenyl (54% Chlorine); D003600:Cytosol / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D000873:Anthracenes; D001140:Aroclors; D009153:Mutagens; D020111:Chlorodiphenyl (54% Chlorine); C006593:2-anthramine