title: The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene.
abstract: 1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR)=1.48, 95% CI: 1.14-1.91, P<0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR=1.70, 95% CI: 1.28-2.27, P<0.01). However, differences in SCE frequency were not observed (FR=1.14, 95% CI: 0.81-1.61, P>0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR=1.35, 95% CI: 1.02-1.80, P<0.05); age, older workers exhibited higher MN frequencies than younger workers (FR=1.45, 95% CI: 1.14-1.84, P<0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR=1.40, 95% CI: 1.10-1.77, P<0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (-) (FR=1.48, 95% CI: 1.14-1.92) or GSTT1 (-) (FR=1.42, 95% CI: 1.10-1.83) genotypes, and especially those who carried both (FR=2.10, 95% CI: 1.43-3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P>0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.
authors.affiliation: The Department of Occupational Health, School of Public Health of Fudan University, and the Key Laboratory of Public Health and Safety of the Ministry of Education of China, Shanghai, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cheng
authors.forename: Tianliang
authors.initials: T
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Jingyang
authors.initials: J
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Shao
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhou
authors.forename: Fanling
authors.initials: F
authors.lastname: Kong
authors.forename: Nannan
authors.initials: N
authors.lastname: Feng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Baode
authors.initials: B
authors.lastname: Shan
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002070:Butadienes / Q000633:toxicity*; D004249:DNA Damage; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange
chemical_list: D002070:Butadienes; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C031763:1,3-butadiene