S-PHENYLCYSTEINE IN ALBUMIN AS A BENZENE BIOMARKER

Biological markers of internal dose are useful for improving the extra polation of health effects from exposures to high levels of toxic air pollutants in animals to low, ambient exposures in humans. Previous re sults from our laboratory have shown that benzene is metabolized by hu mans to form the adduct S-phenylcysteine (SPC). Levels of SPC measured in humans occupationally exposed to benzene were increased linearly r elative to exposure concentrations ranging from 0 to 23.1 ppm for 8 hr /day, 5 days/week. However, the method of measurement used was laborio us, prone to imprecision and interferences, and insufficiently sensiti ve for the low-dose exposures anticipated in the United States (100 pp b>). An improved chemical method was necessary before SPC adducts in a lbumin could be used as a benzene biomarker. A simple, sensitive metho d to measure SPC adducts is being developed and is based on the cleava ge of the cysteine sulfhydryl from blood proteins treated with Raney n ickel (RN) in deuterium oxide. The product of the reaction with SPC is monodeuterobenzene. SPC treated with RN released monodeuterobenzene i n a concentration-dependent fashion. SPC was measured by RN treatment of globin from rats repeatedly exposed by inhalation to 600 ppm benzen e. SPC levels measured using the RN approach were 690+/-390 pmol SPC/m g Hb (mean +/- % difference, n=2), as opposed to 290+/-45 pmol SPC/mg Hb (mean +/- SEM, n=3) as measured by our previous method. This method may facilitate the cast-effective, routine analysis of SPC in large p opulations of people exposed to ambient levels of benzene.