The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene.

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.

[Study on urine biomarkers in 1,3-butadiene exposed workers].

OBJECTIVE: To discuss the urine biomarkers in 1,3-butadiene exposed workers, and to provide basement for establishing biological limit value. METHODS: 44 BD exposed workers as exposure group and 25 BD non-exposed people as control group including 12 workers in boiler workshop in the same factory and 13 people in one public institute, we collected their in-end-of shift urine, then detected urine BD-derived mercapturic metabolites [3,4-dihydroxybutyl mercapturic acid (DHBMA),1- and 2-monohydroxy-3-butenyl mercapturic acid (MHBMA)] concentrations using UPLC-MS/MS method. Meanwhile, we detected air BD concentration with GC-FID in the workplace, and compared their relationship. RESULTS: lgDHBMA and lg (MHBMA + DHBMA) levels in exposed group (lgDHBMA: 2.51 ± 0.44) µg/L, lg [MHBMA + DHBMA: (2.68 ± 0.27) µg/L] were higher than which in control group (lgDHBMA: (2.20 ± 0.25) µg/L, lg(MHBMA + DHBMA: (2.49 ± 0.34) µg/L), and the differences were significant (P < 0.01). Urine DHBMA was obviously influenced by air BD concentrations (r = 0.539, P = 0.001). The equation of Multiple Regression Analysis was y = 2.417 + 0.520x (x represents air BD dose, and represents urinary DHBMA level). Adjusted R(2) of this model was 0.262. Urinary MHBMA was not affected by smoking, alcohol and years of works. CONCLUSION: Urine metabolite DHBMA in BD-exposed workers might be major biological exposure indice.