Superfund Research Program
Development and Application of Biomarkers of Exposure
Project Leader: Stephen M. Rappaport (University of California-Berkeley)
Grant Number: P42ES005948
Funding Period: 1995 - 2011
Over the past year, as part of its investigation of biomarkers of benzene exposure, this project has produced the first unambiguous evidence that benzene oxide (BO) is the primary product of benzene metabolism in rats and is sufficiently stable to be released in significant quantities from hepatocytes into the systemic circulation following metabolism of benzene. It also provides the first evidence that BO produces Hb adducts in humans exposed to benzene and supports the use of BO-Hb as a biomarker of human exposure to benzene. This latter finding arose from collaboration with the National Cancer Institute, which is conducting a major epidemiological investigation of benzene-exposed workers in China.
This project has also shown that differences in metabolism of pentachlorophenol (PCP) in rats and mice lead to different reactive intermediates in the livers of these animals (Cl4-1,2-Benzoquinone and Cl4-1,4-Benzoquinone were the major binding species in mouse liver, whereas in rats Cl4-1,2-Benzosemiquinone and Cl4-1,4-Benzoquinone predominated and no adducts of Cl4-1,2-Benzoquinone were detected). This difference in metabolism leads to much greater binding of reactive intermediates in the nuclei of mouse livers compared to rat livers and offers a plausible explanation of the observation that PCP produces hepatic tumors in mice but not rats.