An epidemiologic study of early biologic effects of benzene in Chinese workers

• Published in: Environmental Health Perspectives [ENVIRON. HEALTH PERSPECT.]. Vol. 104, no. 6 Suppl. Dec 1996 Vol. 104; p. no. 6 Sul.
• Main Authors: Rothman, N, Smith, M T, Hayes, R B, Li, Gui-Lin, Irons, R D, Dosemeci, M, Haas, R, Stillman, W S, Linet, M, Xi, Li-Qiang, Bechtold, W E, Wiemels, J, Campleman, S, Zhang, Luoping
• Format: Conference Proceeding
• Language: English
• Published: 01.12.1996
• Subjects: China, People's Rep
• ISSN: 0091-6765

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cell levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cell levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor- alpha ) in a subset of the most highly exposed workers were similar to values in controls, suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi ) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean plus or minus SD, 13.9 plus or minus 8.4 mutants per million cells versus 7.4 plus or minus 5.2 per million cells, respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.