Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.
Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.
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苯酚类代谢产物的过氧化物酶依赖性代谢及其在苯毒性和致癌性中的潜在作用。
DOI：
10.1289/ehp.898223
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发表时间：
1989-07
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
苯的酚类代谢产物，苯酚和对苯二酚，过氧化物酶的代谢进行了详细的研究。采用辣根过氧化物酶和人髓过氧化物酶的研究表明，在过氧化氢存在下，苯酚转化为4，4 '-联苯醌和其他共价结合代谢物，而氢醌仅转化为1，4-苯醌。令人惊讶的是，苯酚刺激后者的转换，而不是抑制它，效果可能发挥作用，在体内骨髓毒性的苯。事实上，重复共同管理的苯酚和对苯二酚B6 C3 F1小鼠的结果在一个戏剧性的和显着的减少骨髓细胞类似于苯暴露后观察到的。因此，苯诱导的骨髓毒性的机制，其中苯酚和对苯二酚在骨髓中的积累和相互作用以及1，4-苯醌的过氧化物酶依赖的形成是重要的组成部分。这种机制也可能是苯的遗传毒性效应的部分原因，因为1，4-苯醌已被证明会破坏DNA，并在此显示会诱导人类淋巴细胞中的多个微核。因此，骨髓中苯的苯酚代谢物的次级活化可能在苯的骨髓毒性和致癌作用中发挥重要作用。
The metabolism of two of benzene's phenolic metabolites, phenol and hydroquinone, by peroxidase enzymes has been studied in detail. Studies employing horseradish peroxidase and human myeloperoxidase have shown that in the presence of hydrogen peroxide phenol is converted to 4,4'-diphenoquinone and other covalent binding metabolites, whereas hydroquinone is converted solely to 1,4-benzoquinone. Surprisingly, phenol stimulates the latter conversion rather than inhibiting it, an effect that may play a role in the in vivo myelotoxicity of benzene. Indeed, repeated coadministration of phenol and hydroquinone to B6C3F1 mice results in a dramatic and significant decrease in bone marrow cellularity similar to that observed following benzene exposure. A mechanism of benzene-induced myelotoxicity is therefore proposed in which the accumulation and interaction of phenol and hydroquinone in the bone marrow and the peroxidase-dependent formation of 1,4-benzoquinone are important components. This mechanism may also be responsible, at least in part, for benzene's genotoxic effects, as 1,4-benzoquinone has been shown to damage DNA and is shown here to induce multiple micronuclei in human lymphocytes. Secondary activation of benzene's phenol metabolites in the bone marrow may therefore play an important role in benzene's myelotoxic and carcinogenic effects.