Induction of sister chromatid exchanges in human peripheral blood lymphocytes by bromoform: investigation of the role of GSTT1-1 polymorphism

Brominated trihalomethanes (THMs) are disinfection by-products present freq uently in chlorinated drinking water. Brominated THMs are mutagenic in a va riety of systems and are carcinogenic in rodents. The metabolism of bromina ted THMs is thought to involve a GSH conjugation reaction leading either to formaldehyde or DNA-reactive intermediates via glutathione S-transferase-t heta (GSTTI-1), which is polymorphic in humans. In the present study, we ha ve determined the genotoxicity of one of the brominated THMs, bromoform (BF ), by measuring its ability to induce sister chromatid exchanges (SCEs) in whole-blood (WB) cultures of human peripheral blood lymphocytes from GSTT1- 1 + and GSTT1-1 - donors. The results showed no differences in SCEs per cel l by BF between GSTT1-1 + and GSTT1-1 - individuals when the cells were exp osed to 5 X 10(-3) M BF at the beginning of cell culturing (10.8 +/- 0.85 v s. 10.57 + 0.47, respectively), at the 16th (9.66 +/- 0.91 vs. 9.57 +/- 0.0 7), or the 24th h (8.21 +/- 0.61 vs. 8.29 +/- 0.24) of cell growth. Althoug h GSTT1-1 is expressed in the erythrocytes, the lack of expression of the G STT1-1 gene in the target cells (lymphocytes) may account for this observat ion. (C) 1999 Elsevier Science B.V. All rights reserved.