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Folate Deficiency in the Livers of Diethylnitrosamine-treated Rats¹

Department of Nutritional Sciences, University of California, Berkeley, California 94720 [Y. S. S. B., E. L. R. S.], and Carcinogen Metabolism and Toxicology Branch, National Cancer Institute, Bethesda, Maryland 20014 [L. A. P.]

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 diethylnitrosamine 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.

¹ This work was supported by USPHS Grant AM-08171 from the NIH. A preliminary report of this study has been published (35).

² Present address: Kinder Klinik der Universität München, Lindwurm str. 4, 8 Munich 2, W. Germany.

Received 11/17/75. Accepted 4/26/76.