Folate deficiency in the livers of diethylnitrosaminetreated rats

The effects of diethylnitrosamine on the metabolism of folic acid and related compounds in rat liver were investigated. The administration, in the drinking water, of diethynitrosamine to rats for 3 weeks led to decreased hepatic levels of folate, S-adenosylmethionine, and 5-methyltetrahydrofolate:homocysteine methyltransferase. Liver methylenetetrahydrofolate reductase levels were unaffected by administration of diethylnitrosamine. The polyglutamate fraction of hepatic folates obtained from rats treated with diethylnitrosamine for 3 weeks prior to injection with [3H]folate contained less radioactivity than did the polyglutamate fraction obtained from the livers of control rats treated with [3H]folate alone. Similarly, the polyglutamate folate fraction of rat livers that were simultaneously perfused with both diethylnitrosamine and [3H]folate contained less label than the polyglutamate fraction of rat livers perfused with [3H]folate only. Livers perfused with [2-14C]histidine and diethylnitrosamine produced more formiminoglutamate and less CO2 than livers treated with [2-14C]histidine only. The changes noted in the hepatic folate metabolism of diethylnitrosamine-treated rats resemble those seen in the livers of methyl-deficient rats.