A PERSPECTIVE ON BENZENE LEUKEMOGENESIS

Although benzene is best known as a compound that causes bone marrow d epression leading to aplastic anemia in animals and humans, it also in duces acute myelogenous leukemia in humans. The epidemiological eviden ce for leukemogenesis in humans is contrasted with the results of anim al bioassays. This review focuses on several of the problems that face those investigators attempting to unravel the mechanism of benzene-in duced leukemogenesis. Benzene metabolism is reviewed with the aim of s uggesting metabolites that may play a role in the etiology of the dise ase. The data relating to the formation of DNA adducts and their poten tial significance are analyzed. The clastogenic activity of benzene is discussed both in terms of biomarkers of exposure and as a potential indication of leukemogenesis. In addition to chromosome aberrations, s ister chromatid exchange, and micronucleus formation, the significance of chromosomal translocations is discussed. The mutagenic activity of benzene metabolites is reviewed and benzene is placed in perspective as a leukemogen with other carcinogens and the lack of leukemogenic ac tivity by compounds of related structure is noted. Finally, a pathway from exposure to benzene to eventual leukemia is discussed in terms of biochemical mechanisms, the role of cytokines and related factors, la tency, and expression of leukemia.