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 frequently in chlorinated drinking water. Brominated THMs are mutagenic in a variety of systems and are carcinogenic in rodents. The metabolism of brominated THMs is thought to involve a GSH conjugation reaction leading either to formaldehyde or DNA-reactive intermediates via glutathione S-transferase-theta (GSTT1-1), which is polymorphic in humans. In the present study, we have 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 cell by BF between GSTT1-1+ and GSTT1-1- individuals when the cells were exposed to 5 x 10(-3) M BF at the beginning of cell culturing (10.8+/-0.85 vs. 10.57+/-0.47, respectively), at the 16th (9.66+/-0.91 vs. 9.57+/-0.07), or the 24th h (8.21+/-0.61 vs. 8.29+/-0.24) of cell growth. Although GSTT1-1 is expressed in the erythrocytes, the lack of expression of the GSTT1-1 gene in the target cells (lymphocytes) may account for this observation.
Landi
S
S
Environmental Carcinogenesis Division (MD-68), US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. landi.stefano@epa.gov
Hanley
N M
NM
Kligerman
A D
AD
DeMarini
D M
DM
D000328:Adult; D000368:Aged; D002453:Cell Cycle; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005838:Genotype; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange; D013997:Time Factors; D022882:Trihalomethanes
D006842:Hydrocarbons, Brominated; D022882:Trihalomethanes; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D005978:Glutathione; C015044:bromoform