A simple method for assessment of rat cytochrome P-448 isozymes responsible for the mutagenic activation of carcinogenic chemicals.
Cytochrome P-448H/L-enriched and cytochrome P-448L-enriched microsomes were prepared from the livers of Sprague-Dawley rats treated with 3-methylcholanthrene (MC) and with a combination of MC and carbon tetrachloride, respectively, and their activities for mediating mutagenic activation of 9 carcinogenic aromatic amines and benzo[a]pyrene, which are found to be different from cyt. P-450 isozymes as to mutagenic activation, were compared on the basis of microsomal cytochrome P-450 content using Salmonella typhimurium TA98 as a tester bacterium. With regard to the substrate-specificity of cytochrome P-448 isozymes, the present results reflected the reported results with use of a cytochrome P-450-reconstituted system. These findings indicate that the mutation test with cytochrome P-448H/L-enriched and cytochrome P-448L-enriched microsomes could be used as a simple method for the determination of the cytochrome P-448 isozymes responsible for the mutagenic activation of carcinogens and mutagens without the use of a cytochrome P-450-reconstituted system.
Degawa
M
M
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Ueno
H
H
Miura
S
S
Ohta
A
A
Namiki
M
M
D000588:Amines / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D000588:Amines; D002273:Carcinogens; D003580:Cytochromes; D007527:Isoenzymes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital