AN EPIDEMIOLOGIC-STUDY OF EARLY BIOLOGIC EFFECTS OF BENZENE IN CHINESE WORKERS

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into thes e processes, we carried out a cross-sectional study of 44 healthy work ers currently exposed to benzene (median 8-hr time-weighted average, 3 1 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cell levels and soma tic cell mutation frequency measured by the glycophorin A (GPA) gene l oss assay and report on peripheral cytokine levers. All peripheral blo od cell levels (i.e., total while blood cells, absolute lymphocyte cou nt, platelets, red blood cells, and hemoglobin) were decreased among e xposed workers compared to controls, with the exception of the red blo od cell mean corpuscular volume, which was higher among exposed subjec ts. In contrast, peripheral cytokine levels (interleukin-3, interleuki n-6, erythropoietin, granulocyte colony-stimulating factor, tissue nec rosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to Values in controls (n = 11), suggesting that ben zene does not affect these growth factor levels in peripheral blood. T he GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, i dentifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gen e inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 1 3.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million c ells, respectively; p = 0.0002), suggesting that benzene produces gene -duplicating but not gene-inactivating mutations at the GPA locus in b one marrow cells of exposed humans. These findings, combined with ongo ing analyses of benzene macromolecular adducts and chromosomal aberrat ions, will provide an opportunity to comprehensively evaluate a wide r ange of early biologic effects associated with benzene exposure in hum ans.