Recent advances in the metabolism and toxicity of benzene.
Recent advances in the metabolism and toxicity of benzene.
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DOI：
10.3109/10408448709089859
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发表时间：
1987
影响因子：
5.9
通讯作者：
G. Kalf
中科院分区：
文献类型：
--
作者：
G. Kalf
苯是一种大量使用的工业化学品，是石油的副产品，是无铅气体的添加剂，也是一种普遍存在的环境污染物。苯也是一种遗传毒素、血液毒素和致癌物。慢性暴露会导致人类和动物再生障碍性贫血，并与人类白血病和啮齿动物淋巴瘤和某些实体肿瘤的发病率增加有关。苯的毒性需要生物活化。在苯代谢的主要部位肝脏中，苯通过细胞色素P-450介导的途径转化为主要代谢物苯酚和次要代谢物对苯二酚和儿茶酚。苯中毒的靶器官，即造血活跃的骨髓，在非常有限的程度上代谢苯。苯酚在骨髓细胞中通过过氧化物酶介导的途径代谢成对苯二酚和邻苯二酚，最终生成假定的有毒代谢物苯二酚。苯及其代谢物似乎无致突变性，但它们会引起诸如微核、染色体异常和姐妹染色单体互换等骨髓破碎性效应。目前尚不清楚这些基因组变化或苯醌代谢产物与DNA形成加合物的能力是否与苯致癌有关。苯，通过其活性代谢物，似乎通过阻止基质细胞支持各种祖细胞的造血而对骨髓基质微环境产生血液学效应。本文详细介绍了苯的遗传毒性、血液毒性和致癌作用机制的最新研究进展。
Benzene is a heavily used industrial chemical, a petroleum byproduct, an additive in unleaded gas, and a ubiquitous environmental pollutant. Benzene is also a genotoxin, hematotoxin, and carcinogen. Chronic exposure causes aplastic anemia in humans and animals and is associated with increased incidence of leukemia in humans and lymphomas and certain solid tumors in rodents. Bioactivation of benzene is required for toxicity. In the liver, the major site of benzene metabolism, benzene is converted by a cytochrome P-450-mediated pathway to phenol, the major metabolite, and the secondary metabolites, hydroquinone and catechol. The target organ of benzene toxicity, the hematopoietically active bone marrow, metabolizes benzene to a very limited extent. Phenol is metabolized in the marrow cells by a peroxidase-mediated pathway to hydroquinone and catechol, and ultimately to quinones, the putative toxic metabolites. Benzene and its metabolites appear to be nonmutagenic, but they cause myeloclastogenic effects such as micronuclei, chromosome aberrations, and sister chromatid exchange. It is unknown whether these genomic changes, or the ability of the quinone metabolites to form adducts with DNA, are involved in benzene carcinogenicity. Benzene, through its active metabolites, appears to exert its hematological effects on the bone marrow stromal microenvironment by preventing stromal cells from supporting hemopoiesis of the various progenitor cells. Recent advances in our understanding of the mechanisms by which benzene exerts its genotoxic, hematotoxic, and carcinogenic effects are detailed in this review.