Anthraflavic acid inhibits the mutagenicity of the food mutagen IQ: mechanism of action.
The ability of anthraflavic acid to inhibit the mutagenicity of IQ was investigated using the Ames test and employing hepatic activation systems from Aroclor 1254-pretreated rats. Incorporation of anthraflavic acid into the S9 mix caused a concentration-dependent decrease in the mutagenicity of IQ. A similar effect was seen when microsomes only were employed as activation systems. Cytosol, as we have previously demonstrated, potentiated the microsome-mediated mutagenicity of IQ and this potentiation was also inhibited by anthraflavic acid. In contrast, anthraflavic acid had no effect on the mutagenicity of the direct-acting microsome-generated metabolites of IQ. It is concluded that anthraflavic acid is a potent inhibitor of IQ mutagenicity by virtue of its ability to inhibit both its microsomal and cytosolic activation pathways.
Ayrton
A D
AD
Department of Biochemistry, University of Surrey, Guildford, Great Britain.
Ioannides
C
C
Walker
R
R
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D011804:Quinolines / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D000880:Anthraquinones; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes; D007527:Isoenzymes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; C034889:2,6-dihydroxyanthraquinone