Zhang L, Bandy B, Davison A J
Chemistry Department, University of Northern BC, Prince George, Canada.
Free Radic Biol Med. 1996;20(4):495-505. doi: 10.1016/0891-5849(95)02089-6.
1,2,4-Benzenetriol is an active metabolite of the human leukemogen benzene that reacts rapidly with molecular oxygen (O2). The mechanism of autoxidation of benzenetriol is scantily characterized, and little is known of the effects of metals, metal chelators, radical scavengers, and antioxidants on the rate of reduction of O2. Here, we report that catalytic amounts of Cu2+ and Fe3+ accelerated the oxidation of benzenetriol (250 mu M) in a dose-dependent manner. Fe3+ (50 mu M) increased the rate of autoxidation by 91%, and Cu2+ (10 mu M) increased it 11-fold. In the absence of added metals, superoxide dismutase inhibited and desferrioxamine stimulated the autoxidation. In the Cu2+ -catalyzed reaction, superoxide dismutase neither inhibited nor stimulated, while desferrioxamine abolished the catalysis by Cu2+. In the presence of Fe3+, superoxide dismutase slowed the reaction, but desferrioxamine, surprisingly, did not. The presence of both superoxide dismutase and desferrioxamine blocked the autoxidation, either in the presence or absence of metals. We conclude: (1) superoxide is a propagator of sequential one-electron transfer reactions in the absence of added metals; (2) addition of Cu2+, unlike Fe3+, removes the dependence of the reaction on propagation by superoxide, presumably changing the radical-propagated chain reaction to a concerted two-electron transfer; (3) the further addition of desferrioxamine restores superoxide-dependent propagation. Taken with our previous data on the genotoxicity of benzenetriol, these findings have implications regarding a role for transition metals in the carcinogenicity of benzene.
1,2,4-苯三酚是人类白血病致癌物苯的一种活性代谢产物，它能与分子氧（O₂）快速反应。苯三酚的自氧化机制鲜为人知，关于金属、金属螯合剂、自由基清除剂和抗氧化剂对O₂还原速率的影响也知之甚少。在此，我们报告催化量的Cu²⁺和Fe³⁺以剂量依赖的方式加速了苯三酚（250 μM）的氧化。Fe³⁺（50 μM）使自氧化速率提高了91%，而Cu²⁺（10 μM）使其提高了11倍。在不添加金属的情况下，超氧化物歧化酶抑制自氧化，而去铁胺则刺激自氧化。在Cu²⁺催化的反应中，超氧化物歧化酶既不抑制也不刺激，而去铁胺则消除了Cu²⁺的催化作用。在有Fe³⁺存在时，超氧化物歧化酶减缓了反应，但令人惊讶的是，去铁胺却没有。无论是否存在金属，超氧化物歧化酶和去铁胺同时存在时都能阻止自氧化。我们得出以下结论：（1）在不添加金属的情况下，超氧化物是连续单电子转移反应的传播者；（2）与Fe³⁺不同，添加Cu²⁺消除了反应对超氧化物传播的依赖性，推测是将自由基传播链反应转变为协同双电子转移；（3）进一步添加去铁胺可恢复超氧化物依赖性传播。结合我们之前关于苯三酚遗传毒性的数据，这些发现对过渡金属在苯致癌性中的作用具有启示意义。
