DNA adducts of 1,3-butadiene in humans: relationships to exposure, GST genotypes, single-strand breaks, and cytogenetic end points.
The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and cytogenetic end points was studied in 15 workers and 11 controls. The exposed group consisted of 8 smokers and 7 nonsmokers, whereas the control group consisted of 7 nonsmokers and 4 smokers. Among all subjects, the adduct levels in workers lacking GSTM1 were significantly higher than in those who were GSTM1 positive (P = 0.026), and individuals with combined GSTM1(-) and GSTT1(+) genotype had elevated level of adducts compared to that of persons with GSTM1(+) and GSTT1(+) (P = 0.049). The increase in BD-DNA adduct levels in all subjects was significantly related to BD exposure and GSTM1 genotype (linear multiple regression analysis, P = 0.001; P = 0.035). The results suggest that DNA adducts serve as a sensitive and specific biomarker, integrating exposure and host metabolic capacity, although the data are limited to a small number of subjects.
Zhao
C
C
Center for Nutrition and Toxicology, Department of Biosciences, Karolinska Institute, NOVUM, Huddinge, Sweden. chunyan.zhao@cnt.ki.se
Vodicka
P
P
Sram
R J
RJ
Hemminki
K
K
D000328:Adult; D002070:Butadienes / Q000009:adverse effects*; D016022:Case-Control Studies; D020732:Cytogenetic Analysis; D018736:DNA Adducts / Q000097:blood*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000494:pharmacology; D016273:Occupational Exposure; D012044:Regression Analysis; D012907:Smoking
D002070:Butadienes; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D005982:Glutathione Transferase; D009153:Mutagens; C413545:glutathione S-transferase T1; C031763:1,3-butadiene