Firozi P F, Bhattacharya R K
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
J Biochem Toxicol. 1995 Feb;10(1):25-31.
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.
在含有纯化细胞色素P450和NADPH-细胞色素P450还原酶的重组微粒体单加氧酶系统催化下，观察到黄曲霉毒素B1与DNA之间共价加合物的形成受到某些天然来源的多酚类化合物的抑制。发现多羟基黄酮比酚酸更有效，并且表现出剂量依赖性抑制。通过增加细胞色素P450的量可以逆转这种抑制（50%），但增加还原酶的量则不能。通过细胞色素C的还原测定，每种多酚都抑制NADPH-细胞色素P450还原酶活性。用更高量的细胞色素C可以逆转这种抑制。然而，如果使用人工电子受体二氯酚靛酚代替细胞色素C，则这种抑制不能被逆转。这些结果表明多酚对细胞色素具有很强的亲和力。这一结论进一步得到以下观察结果的支持：在重组系统中，用每种多酚预处理细胞色素P450会降低其催化黄曲霉毒素B1-DNA加合物形成的能力。因此，天然多酚可能具有通过调节细胞色素P450功能来调节化学致癌作用的能力。
