EFFECTS OF NATURAL POLYPHENOLS ON AFLATOXIN B-1 ACTIVATION IN A RECONSTITUTED MICROSOMAL MONOOXYGENASE SYSTEM

Covalent adduct formation between aflatoxin B-1 and DNA, as catalyzed by a reconstituted microsomal monooxygenase system containing purified cytochrome P450 and NADPH-cytochrome P450 reductase, was observed to be inhibited by certain polyphenolic compounds of natural origin. Poly hydroxylated flavonoids were found to be more effective than phenolic acids and displayed dose-dependent inhibition. The inhibition (50%) co uld be reversed by increasing the amount of cytochrome P450 but not by increasing the amount of reductase. Each polyphenol inhibited NADPH-c ytochrome P450 reductase activity as measured by reduction of cytochro me C. This inhibition could be reversed with higher amounts of cytochr ome C. This inhibition, however, could not be reversed if an artificia l electron acceptor, dichlorophenolindophenol, was used in place of cy tochrome C. These results suggest a strong affinity of polyphenols tow ard cytochromes. This conclusion was further supported from the observ ation that pretreatment of cytochrome P450 with each polyphenol reduce d its ability to catalyze aflatoxin B-1-DNA adduct formation in the re constituted system. Natural polyphenols, thus, may have the ability to modulate chemical carcinogenesis by modulating cytochrome P450 functi on.