Benzene's toxicity: a consolidated short review of human and animal studies by HA Khan.
Khan's review is a brief summary of the complex field of study revolving around bone marrow toxicity and leukemogenesis observed in people chronically exposed to benzene. These comments are intended to demonstrate the use of the Kahn review as a launching pad for an in-depth analysis of the several related areas that must be fully explored to understand benzene-related diseases. The accumulated evidence demonstrates that benzene-induced bone marrow damage results from the production of hematotoxins that are metabolic products of benzene metabolism. The metabolism of benzene is described with respect to the formation benzene metabolites with emphasis on phenol and hydroquinone, which are the major metabolites, the significance of the formation of glutathione conjugates, the activity of NAD(P)H:quinone oxidoreductase (NQO1), and the ring opening products. Results are shown suggesting that oxidative stress induced by benzene metabolites is likely to be a significant factor in damaging DNA in bone marrow cells. Although a variety of effects on bone marrow can be demonstrated it is not yet clear which metabolites are most important in either benzene-induced aplastic anemia or leukemia. Benzene metabolism alone is insufficient to fully describe benzene toxicity. The impact of benzene metabolites on bone marrow cells must be fully explored to determine how benzene exposure can result in decreased viability or genetic toxicity to cells in the bone marrow.
Snyder
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Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. rsnyder@eohsi.rutgers.edu
D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002869:Chromosome Aberrations / Q000139:chemically induced; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000139:chemically induced; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019800:Phenol / Q000633:toxicity; D018570:Risk Assessment; D018675:Toxicity Tests
D004785:Environmental Pollutants; D006873:Hydroquinones; D009153:Mutagens; D019800:Phenol; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone); D005978:Glutathione; D001554:Benzene; C031927:hydroquinone