The influence of polymorphisms of xenobiotic-metabolizing and DNA repair genes in DNA damage, telomere length and global DNA methylation evaluated in open-cast coal mining workers

摘要

Coal plants represent one of the main sources of environmental pollution due to the combustion process of this mineral and the consequent release of gases and particles which, in significant quantities, can lead to a potential risk to health and the environment. The susceptibility of individuals to the genotoxic effects of coal mining can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. The aim of this study was to evaluate if xenobiotic metabolism polymorphism, base excision repair polymorphisms and nonhomologous end joining repair polymorphism, could modify individual susceptibility to genomic instability and epigenetic alterations induced in workers by occupational exposure to coal. In this study, polymerase chain reaction was used to examine the polymorphic sites. The sample population comprising 70 coal mine workers and 71 workers non-exposed to coal. Our results demonstrated the effect of individual genotypes on different biomarkers evaluated. Significant decrease in % of global DNA methylation were observed in CYP1A1 Val/-exposed individuals compared to CYP1A1 Ile/Ile individuals. Coal workers who carried the XRCC4 Ile/Ile genotype showed decrease NBUD frequencies, while the XRCC4 Thr/- genotype was associated with decrease in Buccal micronucleus cells for the group not exposed. No influence of GSTM1 null, GSTT1 null, GSTP1 Ile105Val, hOGG1 Ser326Cys, XRCC1 Arg194Trp polymorphisms was observed. Thus, the current study reinforces the importance of considering the effect of metabolizing and repair variant genotypes on the individual susceptibility to incorporate DNA damage, as these processes act in a coordinated manner to determine the final response to coal exposure.