Influência do radônio e partículas alfa na oxidação do genoma e metilação das sequências LINE-1

Abstract

The present work aimed to evaluate the genotoxic and epigenetic effects in individuals exposed to natural concentrations of radon (Rn) inside dwellings from Lajes Pintadas city, Rio Grande do Norte state, Brasil. Epigenetic effects were also investigated in assays with cell cultures exposed to different doses of alpha particles. For that purpose, an observational case-control study was conducted with 224 individuals from Lajes Pintadas (LP group) and 66 individuals from Natal city (control group). Blood and urine samples were collected from participants of both cities to perform the following tests: (a) biochemical clinical analysis tests; (b) quantification of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine; (c) determination of the Ser326Cys polymorphism in hOGG1 gene; (d) quantification of lead in blood; (e) quantification of methylated cytosines (mC) in LINE-1 sequences as bioindicators of global genome methylation of the participant’s blood cells. In addition, all recruited individuals were interviewed with a questionnaire to collect sociodemographic information, environmental and occupational exposures, lifestyle and general health history. Besides, measurements of Rn concentrations were collected inside dwellings of participants from both groups. About the in vitro experiments, human lung fibroblasts were exposed to 0 (control), 0.25, 0.5 and 1 Gy of alpha particles and their %mC in the promoter region of the LINE-1 sequences were determined. This assay was repeated for the progeny of irradiated cells. It was observed that individuals exposed to high indoor Rn levels had 8-OHdG concentrations approximately 1.5 times higher than those exposed to low levels of this gas (pvalue < 0.01). People heterozygous for the hOGG1 polymorphism had significantly lower concentrations of 8-OHdG compared to those homozygous for the wild-type allele, considering exposure to the highest Rn levels (from 145 Bq/m3 upwards; p-value < 0.05). The mean concentrations of blood lead between the control and LP groups showed no significant difference: 1.15 ± 0.91 µg/dL and 1.66 ± 1.55 µg/dL, respectively, and these values were below the limit established by the Center Disease Prevention Control (5 µg/dL). In epigenetics, there was a significant difference between the means of %mC in LINE-1 of the groups – 50.23% ± 3.44 for control and 51.87% ± 2.96 for the LP group (p-value < 0.001). Indoor Rn levels, blood lead concentrations and the individuals’ sex were factors that significantly influenced the mean %mC of LINE-1 sequences of the participants. For the in vitro assays, there was no significant difference between the means of %mC among the different doses of alpha particles applied to the cells. It can be concluded that high levels of natural ionizing radiation can cause genome instability through oxidative and epigenetic pathways even in passenger non-irradiated cells from the human body.