Morgan Gareth J, Alvares Caroline L
Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK.
Chem Biol Interact. 2005 May 30;153-154:217-22. doi: 10.1016/j.cbi.2005.03.025. Epub 2005 Apr 12.
The emerging understanding of the biology of the hemopoietic stem cell is beginning to shed light on the mechanisms by which benzene gives rise to acute myeloid leukaemia. These mechanisms are complex, affecting not only the DNA, but also the complex intercellular interactions present in the bone marrow microenvironment. The toxic effects of benzene are mediated within the bone marrow and we are beginning to understand the contributions of inter-individual variation in xenobiotic metabolisms and DNA repair to the definition of risk following exposure to benzene in the environment. This process is likely to be accelerated by recent advances in high throughput genotyping. Until now, research has focussed directly on mutation and chromosomal translocations, but we are beginning to understand more how environmental exposures can modify chromatin structure giving rise to heritable changes not affecting DNA. These epigenetic studies are likely to give important further insights into the mode of action of benzene as are studies of its effect on the immune system.
对造血干细胞生物学的新认识开始揭示苯引发急性髓系白血病的机制。这些机制很复杂，不仅影响DNA，还影响骨髓微环境中存在的复杂细胞间相互作用。苯的毒性作用在骨髓内介导，我们开始了解个体间外源性代谢和DNA修复的差异对环境中接触苯后风险定义的影响。高通量基因分型的最新进展可能会加速这一进程。到目前为止，研究直接集中在突变和染色体易位上，但我们开始更多地了解环境暴露如何改变染色质结构，从而产生不影响DNA的可遗传变化。这些表观遗传学研究以及对苯对免疫系统影响的研究可能会进一步深入了解苯的作用模式。
