You are here:
BENZENE OXIDE PROTEIN ADDUCTS AS BIOMARKERS OF BENZENE EXPOSURE
Citation:
Lindstrom, A B., S. Waidyanatha, K. YeowellO'Connell, AND S. M. Rappaport. BENZENE OXIDE PROTEIN ADDUCTS AS BIOMARKERS OF BENZENE EXPOSURE. Presented at EPA/NIEHS In-House Workshop Biomarkers: Taking Stock, Chapel Hill, NC, August 30-31, 1999.
Description:
Benzene is known to be hematotoxic and carcinogenic in animals and humans. While metabolism is required for toxicity, the identity of the ultimate carcinogen(s) remains unknown. Benzene oxide (BO) is the first and most abundant of the metabolites, but very little is known about its production, disposition, or toxicity. As described below, a variety of techniques were used to investigate fundamental aspects of BO metabolism, with a principal goal being a determination of the tissue dose to the blood and bone marrow following exposure to benzene. In initial experiments the overall reactivity of BO in the blood of mice, rats, and humans was determined. Benzene was then administered to rats and the time-dependent BO concentrations in blood were measured, providing the first unambiguous demonstration that BO was produced and distributed throughout the body via the bloodstream. The second-order rates of reaction for BO with the cysteine thiol groups of hemoglobin (Hb), albumin (Alb), and bone marrow proteins were estimated thereby providing a means to predict the BO tissue dose using BO-protein adduct levels determined in animal and human studies. To further assess BO production and distribution, microsomes from various tissues of control and acetone-treated rats were prepared and used in experiments to examine potential BO production. Additional experiments conducted to examine the origins of background BO-protein adducts indicated that common oxidative reactions can activate benzene and endogenous metabolites to produce reactive species which ultimately form protein adducts identical to those formed with BO.