Benzene Induces Cytotoxicity without Metabolic Activation
Benzene Induces Cytotoxicity without Metabolic Activation
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DOI：
10.1539/joh.10-002-oa
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发表时间：
2011-03-01
影响因子：
3
通讯作者：
Takeuchi, Toru
中科院分区：
文献类型：
--
作者：
Nishikawa, Takuro;Izumo, Kimiko;Takeuchi, Toru
苯在没有代谢活化的情况下诱导细胞毒性：Takuro NISHIKAWA，et al.鹿儿岛大学研究生院医学和牙科科学研究科环境医学和儿科学部门-目的：苯一直与血液系统疾病有关，包括急性髓性白血病和再生障碍性贫血，但引起这些疾病的机制仍不清楚。苯的各种代谢产物通过产生活性氧、抑制拓扑异构酶和损伤DNA等途径产生毒性。然而，苯本身被认为没有致突变或细胞毒性活性。在这项研究中，我们研究了苯本身对人骨髓细胞系的影响，有或没有苯代谢酶抑制剂。方法：人髓系细胞系HL-60暴露于苯，加入或不加入细胞色素P450 2 E1或髓过氧化物酶抑制剂。根据整体DNA甲基化水平、细胞凋亡诱导和ROS产生来评价细胞毒性。结果：苯没有改变整体DNA甲基化水平。然而，苯本身增加了细胞凋亡和活性氧的水平。这种细胞毒性没有改变与苯代谢酶抑制剂的加入。苯本身增加了氧化应激相关基因和激活蛋白-1转录因子的mRNA水平。结论：苯对HL-60细胞DNA甲基化水平无影响，但有细胞毒性作用，并改变基因表达水平。为了阐明苯的毒性机制，必须研究苯本身以及苯的代谢产物。（J Occup Health 2011; 53：84-92）
Benzene Induces Cytotoxicity without Metabolic Activation: Takuro NISHIKAWA, et al. Departments of Environmental Medicine and Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University-Objectives: Benzene has been consistently associated with hematological disorders, including acute myeloid leukemia and aplastic anemia, but the mechanisms causing these disorders are still unclear. Various metabolites of benzene lead to toxicity through the production of reactive oxygen species (ROS), the inhibition of topoisomerase and DNA damage. However, benzene itself is considered to have no mutagenic or cytotoxic activity. In this study, we investigated the effects of benzene itself on a human myeloid cell line with or without benzene metabolizing enzyme inhibitors. Methods: A human myeloid cell line, HL-60, was exposed to benzene with or without cytochrome P450 2E1 or myeloperoxidase inhibitor. Cytotoxicity was evaluated in terms of global DNA methylation levels, induction of apoptosis, and ROS production. Results: Benzene did not change global DNA methylation levels. However, benzene itself increased the levels of apoptosis and ROS. This cytotoxicity did not change with the addition of benzene metabolizing enzyme inhibitors. Benzene itself increased the mRNA levels of oxidative stress-related genes and transcription factors of activator protein-1. Conclusions: Benzene did not influence global DNA methylation in HL-60 cells, but had cytotoxic effects and changed gene expression levels. To elucidate the mechanisms of benzene toxicity, benzene itself as well as benzene metabolites must be investigated. (J Occup Health 2011; 53: 84-92)