Prostaglandin H synthase catalyzed oxidation of hydroquinone to a sulfhydryl-binding and DNA-damaging metabolite.
Prostaglandin H synthase catalyzed oxidation of hydroquinone to a sulfhydryl-binding and DNA-damaging metabolite.
复制标题
前列腺素 H 合酶催化对苯二酚氧化成巯基结合和 DNA 损伤的代谢物。
DOI：
10.1021/tx00016a010
复制
发表时间：
1990
影响因子：
4.1
通讯作者：
Kalf,GF
中科院分区：
文献类型：
--
作者：
Schlosser,MJ;Shurina,RD;Kalf,GF
苯是一种广泛使用的工业化学品和环境污染物，已知会导致职业暴露工人再生障碍性贫血、淋巴细胞减少症和白血病的发生率增加（1，2）。对苯二酚是苯的肝脏代谢物（3），在大鼠暴露于苯后会在骨髓中浓缩（4）。已知对苯二酚给药可诱导小鼠骨髓中的微核（5，6），抑制红细胞生成（7），并降低从骨髓和脾脏中清除的功能性B淋巴细胞的数量（8）。对苯二酚还可引起培养的淋巴细胞中的姐妹染色单体交换（9），导致DNA链断裂（10），并抑制DNA和RNA的合成（11-13）。很可能，即使不是所有这些作用，也有许多是由容易与硫醇、蛋白质和核酸结合的氢醌氧化产物1，4-苯醌和1，4-苯醌介导的（14-19）。对苯二酚在中性pH下自动氧化形成1，4-苯半醌，其可不成比例地转化为1，4-苯醌（20，21）。辣根过氧化物酶（HRP）1还催化氢醌的氧化，以比自氧化快得多的速率通过1，4-苯醌产生1，4-苯醌（20，21），并已显示可将氢醌活化为与细胞蛋白质不可逆结合的代谢物（22）。来自中性粒细胞或巨噬细胞的白细胞过氧化物酶也激活
Benzene is a widely used industrial chemical and en-vironmental pollutant known to cause an increased inci-dence of aplastic anemia, lymphocytopenia, and leukemia in occupationally exposed workers (1, 2). Hydroquinone, a hepatic metabolite of benzene (3), concentrates in bone marrow following exposure of rats to benzene (4). Ad-ministration of hydroquinoneto mice is known to induce micronuclei in bone marrow(5, 6), inhibit erythropoiesis (7), and lower thenumber of functional B-lymphocytes removed from marrow and spleen (8). Hydroquinone also causes sister chromatid exchanges in cultured lymphocytes (9), results in DNA strand breaks (10), and inhibits the synthesis of DNA and RNA (11-13). It is likely that many if not all these effects are mediated by the hydroquinone oxidation products, 1, 4-benzosemiquinone and 1, 4-benzo-quinone, which readily bind to thiols, proteins, and nucleic acids (14-19).Oxidation of hydroquinone to 1, 4-benzosemiquinone and 1, 4-benzoquinone can occur both enzymatically and non-enzymatically. Hydroquinone autoxidizes at neutral pH to form 1, 4-benzosemiquinone which can disproportionate to 1, 4-benzoquinone (20, 21). Horseradish peroxidase (HRP) 1 also catalyzes the oxidation of hydroquinone, yielding 1, 4-benzoquinone via 1, 4-benzosemiquinone at rates much faster thanautoxidation (20, 21), and has been shown to activate hydroquinone to metabolites that bind irreversibly to cellular protein (22). Leukocyte peroxidase from either neutrophils or macrophages also activates