Superfund Research Program
Possible Explanation for Disease Susceptibility to Benzene Exposure
Benzene is a ubiquitous environmental contaminant that is present at many Superfund sites. The general public routinely comes into contact with benzene through gasoline use and tobacco smoke, and thousands of industrial workers encounter significant levels of the compound in the workplace. Presently, there is heightened public concern over the presence of benzene in the environment because it is strongly associated with an increased risk of leukemia and lymphoma in humans exposed occupationally.
While benzene is a significant public health concern, it has been difficult to set uniform occupational and environmental standards that adequately protect all people because humans appear to exhibit differing sensitivities to the compound. Multiple clinical reports suggest that people vary greatly in their susceptibility to the adverse hemotoxic and carcinogenic effects of benzene exposure. Scientists at the University of California at Berkeley recently released the first report of evidence that links inter-individual variation in metabolic processes to an increased risk of a benzene-associated disease. This finding is providing the much needed insight on the observed susceptibility differences of benzene-mediated diseases.
In a collaborative effort with National Cancer Institute, University of Colorado and Chinese investigators, Berkeley scientists carried out a cohort study of 11,177 benzene-exposed workers in Shanghai, China in which benzene poisoning was determined to be a risk factor for hematological malignancy. The impact of inter-individual variation in enzymes that activate and detoxify benzene and its metabolites was assessed in a case-control study of this population. An evaluation of the potential susceptibility factors for benzene poisoning was undertaken in 50 cases of benzene poisoning and 50 controls. Scientists found that metabolic variation was present in two key enzymes involved in benzene metabolism - CYP2E1 (cytochrome P450 2E1) and NQO1 (NADPH:quinone oxidoreductase). Based on these findings, the scientists hypothesize that high CYP2E1 and low NQO1 activity confer an increased susceptibility to benzene poisoning and, therefore, hematological malignancy. CYP2E1 is necessary to convert benzene to benzene oxide, which spontaneously forms phenol and is further metabolized by CYP2E1 to hydroquinone. Hydroquinones are further metabolized to hemotoxic and genotoxic benzoquinones by myleoperoxidase in the bone marrow. NQO1 converts benzoquinones to less toxic metabolites.
These findings contribute significantly to an understanding of the underlying risk factors related to benzene associated diseases. Although people vary in their responses to benzene exposure, the biological underpinnings of the variation have not yet been determined. The results of this study provide timely and necessary information regarding a possible biological mechanism for the observed inter-individual variations in sensitivity to benzene.
Assessing the health risks that benzene poses to humans has been ongoing for several years and there is currently some debate over environmental and occupational standards for the compound. The data that is provided in this study will aid in a more accurate estimation of the risks that benzene poses to humans. In turn this will allow society to better evaluate hazardous site cleanup levels for benzene and set appropriate standards for environmental and occupational exposures to the compound.
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To learn more about this research, please refer to the following sources:
- Rothman N, Smith MT, Hayes RB, Traver RD, Hoener B, Campleman S, Li G, Dosemeci M, Linet MS, Zhang L, Xi L, Wacholder S, Lu W, Meyer KB, Titenko-Holland N, Stewart JT, Yin S, Ross D. 1997. Benzene poisoning, a risk factor for hematologic malignancy, is associated with the NQ01 609C->T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res 57(14):2839-2842. PMID:9230185
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