摘要
苯能引起急性髓性白血病和其他造血系统恶性疾病。低剂量苯暴露的工人也会出现血液毒性,所以对苯的危害评价一直受到关注,特别是低剂量苯暴露的研究具有重要意义。阐述了苯引起白血病可能的机制,如相关的靶基因和相关通路受到干扰、基因诱导、染色体和表观遗传的改变以及基因组不稳定性增加等等。苯所引起的氧化应激,免疫监视下降,导致白血病干细胞形成及增生。由于苯引起血液毒性的复杂性,对于不能毒性评价的建议使用整合方法,比如对人、动物以及体外干细胞巢模型的毒理基因组学和系统生物学研究。这些研究方法可以帮助揭示苯的毒性机制,有利于发现早期生物标志物,促进苯的毒性评价。
Benzene can induce acute myeloid leukemia and probably other hematological malignancies. At very low exposure level （below OELs in China 6 rag/m^3）, it is still reported that benzene causes hematotoxicity. Therefore, the health risk assessment of benzene exposure, at low levels is needed. This article presents the probable mechanism by which benzene induces leukemia, involving the interference to the targeting of critical genes and pathways, the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability. These effects can be modulated by benzene-induced oxidative stress and reduce immune-surveillance and finally lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. The mechanism of benzene-induced hematotoxicity is very complicated, an integrated approach for benzene risk assessment is recommended. The application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche are suggested. These approaches will help us understand the mechanisms of benzene toxicity and identify the potential biomarkers of exposure, early effect and susceptibility, which will be useful for risk assessment.
出处
《职业卫生与应急救援》
2013年第3期122-125,共4页
Occupational Health and Emergency Rescue
基金
国家自然科学基金项目(编号:81202247)
关键词
苯
白血病
低剂量
氧化应激
生物标志物
毒性机制
Benzene
Leukemia
Low exposure level
Oxidative stress
Biomarkers
Mechanisms of toxicity
