Effects of Sodium Arsenite and Sodium Arsenate on Expression of DNA and Arsenic Methyltransferases in Rats

Objective To investigate the influence on arsenic methyltransferase(As3MT) and DNA methyltransferase(DNMT1,DNMT3A,DNMT3B) mRNA expression in rats liver treated with sodium arsenite and sodium arsenate and seek for the difference of DNA and arsenic methylation and both's correlation between sodium arsenite and sodium arsenate(iAs3+ and iAs5+).Methods Different valence state and doses of arsenic were administrated through drinking water to Wistar rats,male rats were divided into seven group randomly,five in each group,control group(deionized water),sodium arsenite low dose group(1/45 LD50,2.33 mg/kg),moderate dose group(1/15 LD50,6.67 mg/kg),high dose group(1/5 LD50,20.00 mg/kg) administrated with different concentrations of sodium arsenite;sodium arsenate low dose group(1/45 LD50,2.33 mg/kg),moderate dose group(1/15 LD50,6.67 mg/kg),high dose group(1/5 LD50,20.00 mg/kg) administrated with different concentrations of sodium arsenate.The reagents were given through drinking water,for 90 consecutive days.At the end of the third month,the rats were sacrificed to collect the liver,and the expression of DNA and arsenic methyltransferase were detected by real-time PCR in liver genome mRNA.Results The difference of As3MT and DNA methyltransferase mRNA expression in every group was significant(P0.05) compared with the control group;the expression of As3MT mRNA increased and the expression of DNMT3A and DNMT3B mRNA were decreased in arsenic the exposed group;the expression of DNMT1 mRNA increased in high and low iAs3+ exposed group and in high iAs5+ exposed group,the expression of DNMT1 mRNA decreased in moderate iAs3+ exposed group and in low iAs5+ exposed group.With the increasing dose of iAs3+,As3MT mRNA expression showed an increasing trend and DNMT3A and DNMT3B mRNA expression showed a decresing trend in iAs3+ group;with the increase of iAs5+ dose,As3MT mRNA expression showed a decreasing trend and DNMT3A,DNMT3B and DNMT1 mRNA expression showed an increasing trend in iAs5+ group.Meanwhile,by spearman methods the correlation analysis indicated that the level of As3MT mRNA expression in liver correlated negatively with the level of DNMT3A and DNMT3B mRNA expression(P0.01).Conclusion Long-term and chronic exposure to iAs3+ or iAs5+ may induce up-regulated As3MT mRNA expression and down-regulated DNMT3A and DNMT3B mRNA expression with opposite direction existed in the dose-effect relationships between iAs3+ and iAs5+.There is a synergistic effect between the increasing level of As3MT mRNA expression and the decreasing level of DNMT3A and DNMT3B mRNA expression,which may result in gene hypomethylation.