DNA hypomethylation induced by tributyltin, triphenyltin, and a mixture of these in Sebastiscus marmoratus liver.

Tributyltin (TBT) and triphenyltin (TPT) coexist in freshwater and marine environments. However, the effects of TBT, TPT, and a mixture of the two on DNA methylation in marine fish livers and the mechanism involved remain to be elucidated. Previous study have proved that abnormal methylation patterns are induced by the balance of transmethylation reaction including the tissue level of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) or the activity of DNA (cytosine-5) methyltransferase 1 (DNMT1). Therefore, in the present study, we assessed their ability to cause hepatic DNA hypomethylation in Sebastiscus marmoratus liver and the related mechanism. The results showed that TBT, TPT, and a mixture of the two significantly induced DNA hypomethylation in the fish livers in a dose-dependent manner. Using Pearson correlation coefficient analysis, we identified strong linear correlations between S-adenosylhomocysteine, S-adenosylmethionine, or the SAM to SAH ratio and the hepatic genome-wide 5-methylcytosine content of the DNA, but no correlation between the latter and the DNMT1 expression level. It is therefore proposed that the organotins hypomethylation induced in the marine fish livers was due to altering the balance of the substrate and the product in transmethylation reactions.