Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · Feb 2009
Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo in human promyelocytic leukemic cell lines and ex vivo in human blood neutrophils.
Exposure to benzene elicits a spectrum of hematotoxicity ranging from reduction of peripheral blood cell counts to aplastic anemia and leukemia. The molecular mechanism by which benzene damages hematopoietic cells is unclear; in particular, benzene-induced aberrant gene expression has not been addressed. We analyzed differential gene expression in the peripheral white blood cells from seven female patients with occupational benzene poisoning and seven matched control subjects. ⋯ On the other hand, hydroquinone induced extensive apoptosis of the cells. The findings demonstrated, for the first time, that benzene and metabolites induce CYP4F3 in human blood cells both in vivo and in vitro. Induction of CYP4F3 may play a role in the development of benzene hematotoxicity and serve as a biomarker of benzene exposure.