NADPH CYTOCHROME-P-450 REDUCTASE ACTIVATION OF QUINONE ANTI-CANCER AGENTS TO FREE-RADICALS

被引：660

作者：

BACHUR, NR ^{[1
]}

GORDON, SL ^{[1
]}

GEE, MV ^{[1
]}

KON, H ^{[1
]}

机构：

[1] NIAMDD,CHEM PHYS LAB,BETHESDA,MD 20014

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1979年 / 76卷 / 02期

关键词：

D O I：

10.1073/pnas.76.2.954

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The banzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol, and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to molecular oxygen to form superoxide. The overall K(m) range for this electron transfer is 0.4 to 42.1 x 10-4M. we postulate that the formation of the 'site-specific free radical' intermediate is central to the cytotoxic action of these antibiotics.

引用

页码：954 / 957

页数：4

共 30 条

[1]

BACHUR NR, 1970, J PHARMACOL EXP THER, V175, P331

[2]

BACHUR NR, 1970, CANCER CHEMOTH REP 1, V54, P89

[3]

BACHUR NR, 1974, J PHARMACOL EXP THER, V191, P331

[4]

BACHUR NR, 1977, MOL PHARMACOL, V13, P901