Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
School of Environmental Sciences, Queen's University, Kingston, Ontario, Canada.
J Appl Toxicol. 2020 Aug;40(8):1018-1032. doi: 10.1002/jat.3961. Epub 2020 Feb 28.
Benzene is an environmental toxicant found in many consumer products. It is an established human carcinogen and is known to cause acute myeloid leukemia in adults. Epidemiological evidence has since shown that benzene can cross the placenta and affect the fetal liver. Animal studies have shown that in utero exposure to benzene can increase tumor incidence in offspring. Although there have been risk factors established for acute myeloid leukemia, they still do not account for many of the cases. Clearly then, current efforts to elucidate the mechanism by which benzene exerts its carcinogenic properties have been superficial. Owing to the critical role of cell signaling pathways in the development of an organism and its various organ systems, it seems plausible to suspect that these pathways may have a role in leukemogenesis. This review article assesses current evidence of the effects of benzene on critical hematopoietic signaling pathways. Pathways discussed included Hedgehog, Notch/Delta, Wingless/Integrated, nuclear factor-kappaB and others. Following a review of the literature, it seems that current evidence about the effects of benzene on these critical signaling pathways remains limited. Given the important role of these pathways in hematopoiesis, more attention should be given to them.
苯是一种存在于许多消费品中的环境毒物。它是一种已确定的人类致癌物,已知会导致成年人急性髓性白血病。此后的流行病学证据表明,苯可以穿过胎盘并影响胎儿肝脏。动物研究表明,胎儿在子宫内接触苯会增加后代肿瘤的发病率。尽管已经确定了急性髓性白血病的危险因素,但仍不能解释许多病例。显然,目前阐明苯发挥致癌特性的机制的努力还不够深入。由于细胞信号通路在生物体及其各种器官系统的发育中起着关键作用,因此怀疑这些通路可能在白血病发生中起作用似乎是合理的。这篇综述文章评估了苯对关键造血信号通路的影响的现有证据。讨论的途径包括 Hedgehog、Notch/Delta、Wingless/Integrated、核因子-κB 等。在对文献进行回顾后,似乎目前关于苯对这些关键信号通路影响的证据仍然有限。鉴于这些途径在造血中的重要作用,应该给予更多关注。