Effect of trichloroethylene and its metabolites, dichloroacetic acid and trichloroacetic acid, on the methylation and expression of c-jun and c-myc protooncogenes in female B6C3F1 mouse liver: Prevention by methionine

chloroacetic acid (TCA) are environmental contaminants that are carcinogenic in mouse liver. 5-Methylcytosine (5-MeC) in DNA is a mechanism that controls the transcription of mRNA, including the protooncogenes, c-jun and c-myc. We have previously re-ported that TCE decreased methylation of the c-jun and c-myc genes and increased the level of their mRNAs. Decreased meth-ylation of the protooncogenes could be a result of a deficiency in S-adenosylmethionine (SAM), so that methionine, by increasing the level of SAM, would prevent hypomethylation of the genes. For 5 days, female B6C3F1 mice were administered, daily by oral gavage, either 1000 mg/kg body weight of TCE or 500 mg/kg DCA or TCA. At 30 min after each dose of carcinogen, the mice received, by ip injection, 0-, 30-, 100-, 300-, or 450-mg/kg methi-onine. Mice were euthanized at 100 min after the last dose of DCA, TCA, or TCE. Decreased methylation in the promoter regions o