This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yong, L. C. Articles by Ward, E. M. Search for Related Content PubMed PubMed Citation Articles by Yong, L. C. Articles by Ward, E. M.

Hemoglobin Adducts and Sister Chromatid Exchanges in Hospital Workers Exposed to Ethylene Oxide

Effects of Glutathione S-Transferase T1 and M1 Genotypes

Division of Surveillance, Hazard Evaluations and Field Studies [L. C. Y., M. F. B., L. B. C., J. T. W., E. A. W., E. M. W.], Education and Information Division [P. A. S.], National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226, and Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94143 [J. K. W.]

Ethylene oxide (EtO) is a genotoxic carcinogen with widespread uses as an industrial chemical intermediate and sterilant. We examined the effects of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes on the levels of N-(2-hydroxyethyl)valine (HEV) adducts in the erythrocytes and sister chromatid exchange (SCE) in lymphocytes from a group of 58 operators of sterilizers that used EtO and nonexposed workers from nine hospitals in the United States and one hospital in Mexico City. Cumulative exposure to EtO was estimated during the 4-month period before the collection of blood samples. Results showed that EtO exposure was significantly associated with the levels of HEV adducts and SCE after adjusting for cigarette smoking and other potential confounders. A significantly higher HEV adduct level (0.17 ± 0.03 versus 0.08 ± 0.01, mean ± SE; P = 0.02) but lower SCE frequency (5.31 ± 0.39 versus 6.21 ± 0.17; P = 0.04) was observed in subjects with homozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype). In multiple regression analysis, the GSTT1-null genotype was associated with an increase in HEV adduct level (ß = 1.62; P = 0.02) and a decrease in SCE frequency (ß = -1.25; P = 0.003) after adjusting for age, gender, race, education, cigarette smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship remained unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associated with the level of either HEV adduct or SCE. These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobin adducts in relation to occupational EtO exposure, suggesting that individuals with homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of EtO. The unexpected finding of decreased SCEs, which is less clear, may be attributed to the nonchemical specificity of this end point and the lack of expression of the GSTT1 enzyme in lymphocytes.

This article has been cited by other articles:

				E. Taioli AN AUTHOR REPLIES Am. J. Epidemiol., June 15, 2007; 165(12): 1462 - 1463. [Full Text] [PDF]

				V. Haufroid, B. Merz, A. Hofmann, A. Tschopp, D. Lison, and P. Hotz Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 796 - 802. [Abstract] [Full Text] [PDF]

				S Raimondi, V Paracchini, H Autrup, J. Barros-Dios, S Benhamou, P Boffetta, M. Cote, I. Dialyna, V Dolzan, R Filiberti, et al. Meta- and Pooled Analysis of GSTT1 and Lung Cancer: A HuGE-GSEC Review Am. J. Epidemiol., December 1, 2006; 164(11): 1027 - 1042. [Abstract] [Full Text] [PDF]

				D Coggon, E C Harris, J Poole, and K T Palmer Mortality of workers exposed to ethylene oxide: extended follow up of a British cohort Occup. Environ. Med., April 1, 2004; 61(4): 358 - 362. [Abstract] [Full Text] [PDF]