Hemoglobin adducts and sister chromatid exchanges in hospital workers exposed to ethylene oxide: effects of Glutathione S-Transferase T1 and M1 genotypes.
Yong-LC; Schulte-PA; Wiencke-J; Boeniger-MF; Connally-LB; Walker-JT; Whelan-EA; Ward-EM
Cancer Epidemiol Biomark Prev 2001 May; 10(5):539-550
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 (beta = 1.62; P = 0.02) and a decrease in SCE frequency (beta = -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.
Health-care-facilities; Health-care-personnel; Epidemiology; Statistical-analysis; Humans; Genotoxic-effects; Gene-mutation; Cancer; Cancer-rates
Industrywide Studies Branch, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, MS R15, Cincinnati, OH 45226
Cancer Epidemiology, Biomarkers & Prevention