Hemoglobin adducts and sister chromatid exchanges in hospital workers exposed to ethylene oxide: Effects of glutathione S-transferase T1 and M1 genotypes

Ethylene oxide (EtO) is a genotoxic carcinogen,vith widespread uses as an i ndustrial chemical intermediate and sterilant, We examined the effects of g lutathione S-transferase TI (GSTT1) and MI (GSTM1) genotypes on the levels of N-(2-hydroxyethyl) valine (HEV) adducts in the erythrocytes and sister c hromatid exchange (SCE) in lymphocytes from a group of 58 operators of ster ilizers that used EtO and nonexposed workers from nine hospitals in the Uni ted 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 lev els 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 h omozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype), In multiple regres sion analysis, the GSTT1-null genotype was associated with an increase in H EV adduct level (P = 1.62; P = 0.02) and a decrease in SCE frequency (P = - 1.25; P = 0.003) after adjusting for age, gender, race, education, cigarett e smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship rema ined unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associate d,vith the level of either HEV adduct or SCE, These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobi n adducts in relation to occupational EtO exposure, suggesting that individ uals,vith homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of EtO, The unexpected finding of decreased SCEs, whi ch is less clear, may be attributed to the nonchemical specificity of this end point and the tack of expression of the GSTT1 enzyme in lymphocytes.