Lead (Pb) is a toxic metal widely used as a raw material in the industry for the manufacture of rubber, glazes, glass and especially in automotive battery factories where workers are exposed to metal. Due to its potential to produce free radicals and reactive species, Pb can cause damage to the DNA, which, if not correctly repaired, generates cytogenetic damage, such as micronuclei (MNs) and chromosomal aberrations (AC), which is classified as 2A (possibily carcinogen) by IARC (International Agency for Research on Cancer). Currently, the use of effect biomarkers, such as comet and MN tests, that investigate the impact of Pb on exposed individuals are largely used and considered as very important. In addition, polymorphisms in DNA repair genes may alter the functional properties of the enzymes, and consequently, modulate the genotoxicity induced by Pb exposure. Therefore, aims of this project are to evaluate the impact of exposure to metal on DNA stability, as well as possible interactions gene-metal in individuals occupationally exposed to Pb. Metal concentrations will be determined in blood, plasma and urine by ICP-MS. The oxidative DNA damage product (8-OHdG) will be quantified by HPLC-MS / MS. Responses to DNA damage will be evaluated by the Comet Assay, as well as genotoxic effects, changes in cell cycle kinetics, proliferative and cytotoxic potential will be monitored by the oral micronucleus assay (BMCyt). Genotypes of SNP-like polymorphisms of the genes involved in the DNA repair process (OGG1, XRCC1, PARP-1, MLH1, MSH6, MSH2, XPA, XPC e ERCC1) and telomere size will be assessed by qPCR. Thus, it is expected that the results obtained will aid in a better understanding of the mutagenic effects and the role played by genetic variants in the induction of damage induced by exposure to Pb. In addition, this study intends to contribute with a line of research still incipient in the country, but very promising denominated "gene-environment interactions", which may designate possible markers of exposure and effect in individuals occupationally exposed to this metal.
News published in Agência FAPESP Newsletter about the scholarship: