Structure and reactions of oxygenase active centres: cytochrome P-450 and iron-sulphur proteins

作者：IRWIN C. GUNSALUS, John D. Lipscomb, VINCENT P. MARSHALL, Hans Frauenfelder, Eckard Münck, Elias Greenbaum · 发表于：Biochemical Journal · 年份：1971 · DOI：10.1042/bj1250005p · 被引用次数：10 · 研究领域：Redox biology and oxidative stress、Free Radicals and Antioxidants、Hemoglobin structure and function

5Ppresence of aryl hydrocarbon hydroxylase activity;(3) the inhibition of hydroxylase activity in cells by 7,8-benzoflavone is paralleled by an inhibition of the toxic effects of 7,12-dimethylbenz[a]anthracene; (4) 7,8-benzoflavone inhibits the enzyme in mouse skin homogenates and exhibits 7-12-di- methylbenz[a]anthracene-induced skin tumori- genesis.[14C]7,12-Dimethylbenz[a]anthracene forms co- valent linkage to the DNA, RNA and proteins of mouse skin.7,8-Benzoflavone inhibits this binding by 70, 60 and 50% respectively; it inhibits 7,12- dimethylbenz[a]anthracene-initiated tumour form- ation by 50-80% when applied simultaneously with 7,12-dimethylbenz[a]anthracene.No effect is observed when the 7,8-benzoflavone is applied 12 or 24h after the 7,12-dimethylbenz[a]anthracene.Thus the part of the tumour-initiation process inhibited by 7,8-benzoflavone is completed in less than 12-24h.In two different systems of tumori- genesis this inhibitor either has no effect or stimu- lates benzopyrene-induced tumour formation.This suggests that the role of the enzyme vi.8-d-vi8 carcinogen activation and detoxification may be unique for each hydrocarbon.