Abstract

To investigate the relationship between DNA repair gene methylation and chronic coal-burning fluorosis. The methylation rates of O⁶-methylguanine-DNA- methyltransferase gene MGMT, a DNA repair gene and mismatch repair gene MutL homolog 1 (MLH1) were analysed by methylation of specific PCR (MSP), and the levels of mRNA in the blood of the chronic fluorosis rats and the patients in the region of endemic coal-burning fluorosis were determined by real-time PCR. The levels of mRNA and protein of MGMT and MLH1 in the liver tissue of the chronic fluorosis rats were determined by real-time PCR and Western blot respectively. The results showed an increased methylation of the MGMT and MLH1 genes in the blood of the patients in the fluorosis region that correlated positively with the severity of fluorosis. The mRNA levels of MGMT and MLH1 genes from the patients in fluorosis region were lower than those of a control group, and also showed a positive correlation with the severity of fluorosis. Both the protein and mRNA levels of MGMT and MLH1 genes from the blood of rats and liver tissue in a fluoride-treated group were lower than those of a control non-fluoride treated group. These results indicate that the degree of methylation of MGMT and MLH1 genes is altered in fluorosis disease, the resulting changed expression of these repair genes may play a role in the liver damage caused by fluoride.

• Related Studies :

  • Effects of fluoride on DNA damage and caspase-mediated apoptosis in the liver of rats

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver. In this study, we investigated liver histopathology, DNA damage, apoptosis, and the mRNA and protein expressions of caspase-3 and -9 in the rat

  • Protective effects of vitamin C against fluoride toxicity.

    Fluorine is a highly toxic substance that is widely distributed with drinking water and nutrients. While fluorine is not free in nature, it can form compounds with almost all metals and nonmetals except oxygen and inert gases. Fluorine is found in the environment in water, soil, air, nutrients, and vegetation

  • DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes

    AIM:  To study the effect of fluoride on oxidative stress, DNA damage and apoptosis as well as cell cycle of rat oral mucosal cells and hepatocytes. METHODS:  Ten male SD rats weighing 80-120 g were randomly divided into control group and fluoride group, 5 animals each group. The animals in

  • Genotoxicity of fluoride subacute exposure in rats and selenium intervention.

    Highlights Subacute exposure of Wistar rats to fluoride and selenium. Fluoride at a dose of 150 ppm induced DNA damage in the liver, spleen and brain tissue cells, not in blood. Selenium supplementation reduces DNA damage in liver and spleen cells. Fluoride damage did not occur on a histological

  • Studies on the DNA and RNA contents of heart, liver and kidney of rats with chronic fluorosis

    17 rats with chronic fluorosis induced by prolonged drinking of water containing 50 ppm fluorine and 17 rats drinking low-fluorine water served as control were used to study the DNA and RNA contents of heart, liver and kidney. The findings suggest that excessive accumulation of fluorine can suppress the synthesis