Metabolic activation of diethylstilbestrol by stimulated human leukocytes.
Metabolic activation of diethylstilbestrol by stimulated human leukocytes.
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DOI：
10.1016/0304-3835(87)90059-0
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发表时间：
1987-04
期刊：
影响因子：
9.7
通讯作者：
D. Eastmond;R. French;D. Ross;Martyn T. Smith
中科院分区：
文献类型：
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作者：
D. Eastmond;R. French;D. Ross;Martyn T. Smith
以往的研究表明，过氧化物酶和白细胞参与了人类致癌物己烯雌酚（DES）的代谢活化。在这里，我们证明，DES在人白细胞的氧化爆发过程中转化为反应性蛋白结合物种。虽然鲁米诺依赖的化学发光表明，过氧化物酶依赖的代谢发生，蛋白质结合是不可逆的叠氮化物。这表明，无论是过氧化物酶介导的代谢是不负责的反应性蛋白结合物种的形成，或这种结合发生在一个细胞室无法访问叠氮化物。然而，单独添加过氧化氢酶和与超氧化物歧化酶（SOD）组合确实导致结合的显著抑制。次氯酸也被证明能够直接将DES转化为蛋白结合物质。这些结果表明，氧化爆发的产物，最有可能是来自H2O2的高氧化物质，能够将DES转化为潜在致癌的结合物质。
Previous studies have implicated both peroxidases and leukocytes in the metabolic activation of the human carcinogen diethylstilbestrol (DES). Here we demonstrate that DES is converted during the oxidative burst of human leukocytes to reactive protein binding species. Although luminol-dependent chemiluminescence indicated that peroxidase-dependent metabolism was occurring, the protein binding was not inhibitable by azide. This suggested that either peroxidase-mediated metabolism was not responsible for the formation of the reactive protein binding species or that this binding was occurring in a cellular compartment inaccessible to azide. The addition of catalase alone and in combination with superoxide dismutase (SOD) did, however, result in significant inhibition of binding. Hypochlorous acid was also shown to be capable of directly converting DES to protein binding species. These results indicate that a product of the oxidative burst, most likely a highly oxidizing species derived from H2O2, is capable of converting DES to a potentially carcinogenic binding species.