The effects of methionine on TCE-induced DNA methylation and mRNA expression changes in mouse liver

Abstract

Trichloroethylene (TCE) had been shown to induce aberrant DNA methylation changes in mouse liver, which could be critical in the development of hepatocellular carcinoma. To understand the effect of methionine, a methyl donor, on TCE-induced mouse liver cancer, we exposed B6C3F1 mice to TCE in the presence or absence of methionine. We found that supplementation with methionine attenuated the TCE-induced hypo- and hyper-methylation status of Cdkn1a and Ihh in mouse liver, respectively. The TCE-induced mRNA expression changes of Cdkn1a, Ihh and Jun were also alleviated by methionine. However, methionine supplementation accelerated the TCE-induced mRNA over-expression of Mki67, and enhanced the TCE-induced mRNA down-regulation of Dnmt3a and Tet2. In summary, our results showed that methionine could attenuate at least part of the TCE-induced DNA methylation changes, but the additional gene expression changes induced by supplementary of methionine does not support the assumption that methionine could prevent TCE-induced liver carcinogenesis.