Chromosomal aberrations in railroad transit workers: Effect of genetic polymorphisms

Abstract

Complex chemical mixtures are transported by train from Russia to Finland for further shipment. Here, we studied if exposure to genotoxic components among these substances could affect chromosomal aberrations (CAs) in peripheral lymphocytes of workers handling the tank cars. An initial survey among 48 railroad workers and 39 referents (male smokers and nonsmokers) showed an elevation of CAs. A campaign was started to reduce exposures through preventive measures. Five years later, 51 tank car workers and 40 age-matched referents (all nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5, XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR). No increase in CAs was seen in the exposed group, suggesting that the preventive measures had been successful. However, a positive association existed between exposure duration and CA level among the exposed subjects. The level of chromosome-type breaks was actually lower in the exposed workers than the referents, particularly among MTHFR wild-type homozygotes or XRCC3 codon 241 variant allele carriers, suggesting modulation of CA frequency by folate metabolism and DNA repair. An interaction was observed between the occupational exposure and MTHFR, EPHX1, and MTR genotypes in determining CA level. The NAT2, ERCC2 exon 10, and XRCC1 codon 194 polymorphisms also affected CA frequency. Our findings suggest that handling of tank cars containing complex chemical mixtures poses a genotoxic risk, which may be reduced by preventive measures. Several genetic polymorphisms seem to modify the genotoxic effect or baseline CA level.

Folate metabolism modifies chromosomal damage induced by 1,3-butadiene: results from a match-up study in China and in vitro experiments

“…The first of these variants, C677T, has been shown to be associated with higher baseline homocysteine levels in the serum and is associated with increased risk of vascular disease and neural tube defects, and polymorphisms of A1298C may be risky factors of multiple tumors in several studies. In 2008, a study in Beijing area [19] [20,21], suggested that MTHFR gene polymorphisms were associated with individual chromosomal damage. Our results, consistent with these studies, raises the concerns that the effect of occupational exposure to BD may be significantly modulated by folate status which varies greatly amongst individuals.…”