Effects of natural polyphenols on aflatoxin B1 activation in a reconstituted microsomal monooxygenase system.
Covalent adduct formation between aflatoxin B1 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. Polyhydroxylated flavonoids were found to be more effective than phenolic acids and displayed dose-dependent inhibition. The inhibition (50%) could be reversed by increasing the amount of cytochrome P450 but not by increasing the amount of reductase. Each polyphenol inhibited NADPH-cytochrome P450 reductase activity as measured by reduction of cytochrome C. This inhibition could be reversed with higher amounts of cytochrome C. This inhibition, however, could not be reversed if an artificial electron acceptor, dichlorophenolindophenol, was used in place of cytochrome C. These results suggest a strong affinity of polyphenols toward cytochromes. This conclusion was further supported from the observation that pretreatment of cytochrome P450 with each polyphenol reduced its ability to catalyze aflatoxin B1-DNA adduct formation in the reconstituted system. Natural polyphenols, thus, may have the ability to modulate chemical carcinogenesis by modulating cytochrome P450 function.
Firozi
P F
PF
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
Bhattacharya
R K
RK
D015086:2,6-Dichloroindophenol / Q000378:metabolism; D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000502:physiology*; D009251:NADPH-Ferrihemoprotein Reductase; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D003574:Cytochrome c Group; D018736:DNA Adducts; D005419:Flavonoids; D010636:Phenols; D010713:Phosphatidylcholines; D011108:Polymers; C072611:aflatoxin B1-DNA adduct; C015153:1,2-dilauroylphosphatidylcholine; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D015086:2,6-Dichloroindophenol; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D009245:NADH Dehydrogenase