Overview of benzene-induced aplastic anaemia.

The scientific literature is replete with reports of cases of benzene-induced toxicity to the haematopoietic system. These mainly involve aplastic anaemia, the first cases of which were reported in 1897. At high level of benzene exposure (air concentration > 100 p.p.m.), the incidence of aplastic anaemia is approximately 1/100 individuals exposed, but this drops precipitously at lower levels of exposure (10-20 p.p.m.) to around 1/10,000. Factors that affect susceptibility may include high liver cytochrome P450 2E1 activity and low folic acid intake. The mechanism of benzene-induced aplastic anaemia remains unclear, but is likely to involve: (a) metabolism of benzene in the liver; (b) transport of metabolites to the marrow and their secondary activation to toxic quinones and free radicals by peroxidase enzymes; (c) induction of apoptosis, DNA damage and altered differentiation in early progenitor cells; and (d) depletion of the stem cell pool.