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Our previous studies have shown that cancer mortality in high background-radiation areas of China was lower than that in a control area, indicating the possibility of an adaptive response in high background-radiation areas. Our aim is to determine the effect of low-dose radiation on the level of DNA oxidative damage, DNA damage repair, antioxidant capacity, and apoptosis in high background-radiation area and control area populations of Guangdong through a molecular epidemiological study in order to identify adaptive response. Blood samples were collected from male residents aged 50 to 59 y in a high background-radiation area (Yangjiang) and a control area (Enping), and activities of superoxide dismutase, glutathione, catalase, total antioxidant capacity, and expression of O6‐methylguanine-DNA methyltransferase gene (MGMT), human 8‐oxoguanine DNA N-glycosylase 1 gene (hOGG1), proapoptotic genes and antiapoptotic genes, oxidative-stress-related genes, as well as concentrations of 8‐OHdG, TrxR, HSP27, and MT-COX2 were determined. The activities of antioxidative enzymes, relative mRNA expression level of DNA repair genes, antiapoptotic genes, oxidative-stress-related genes HSPB1 and MT-COX2, and the concentration of antioxidant index TrxR in the high background-radiation area population increased significantly compared to the control population (p < 0.05). The relative mRNA expression level of proapoptotic genes and the concentration of DNA oxidative damage index 8‐OHdG were significantly lower in the high background-radiation area compared to those in the control area (p < 0.05). In conclusion, under long-term, natural, high background, ionizing radiation, DNA damage-repair capacity and antioxidant capacity of inhabitants in the high background-radiation area may be enhanced. Additionally, it could induce up regulation of cell-survival gene expression and down regulation of apoptotic gene expression. It might be speculated that enhanced antioxidant and DNA repair capacity and inhibition of apoptosis might play important roles in adaptive response of low-dose radiation in high background-radiation areas.