Folate Deficiency in Rats Bearing the Walker Tumor 256 and the Novikoff Hepatoma¹ Free

A folate deficiency was noted in rats bearing the Novikoff hepatoma and the Walker 256 carcinosarcoma. The deficiency was determined by an elevated urinary excretion of the histidine catabolite, formiminoglutamic acid, following a loading dose of histidine to the tumor-bearing rats. The folate deficiency of the tumor-bearing rats could not be attributed to altered patterns of dietary consumption or of hepatic histidine-catabolizing enzymes. Further, the oligoglutamate folate fraction of the livers of rats bearing the Novikoff hepatoma was essentially identical to that of normal rats. The elevated formiminoglutamic acid excretion by rats bearing the Novikoff hepatoma could be reversed by high dietary levels of methionine and choline. High dietary levels of folate and of vitamin B₁₂, alone or in combination, had no effect on the elevated formiminoglutamic acid excretion by the hepatoma-bearing rats; similarly, the addition of glycine, serine, formate, thymine, adenine, and guanine to the diets of rats bearing the Novikoff hepatoma did not diminish the elevated urinary formiminoglutamic acid levels. The results indicate that the folate deficiency of tumor-bearing animals may be the consequence of an excessive requirement for methyl groups in the host-tumor system.