Benzene and the hemopoietic stem cell.
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.
Morgan
Gareth J
GJ
Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. gareth.morgan@rmh.nthames.nhs.uk
Alvares
Caroline L
CL
D000208:Acute Disease; D001554:Benzene / Q000633:toxicity*; D004781:Environmental Exposure; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000235:genetics
D001554:Benzene