Effect of Folate and Cobalamin Compounds on the Deoxyuridine Suppression Test in Vitamin B12 and Folate Deficiency

Abstract

In vitro, deoxyuridine (dU) failed to block the incorporation of 3H-thymidine into bone marrow from 11 cases of vitamin B,2 deficiency, 6 cases of folate deficiency, an'i 3 cases of combined deficiency, even in patients without overt anemia, macro- cytosis, and/or megaloblastosis. Different folate and cobalamin compounds had different effects on the incorporation of 3H-thymidine in the two deficiencies. In folate deficiency, the suppressive effect of dU became normal with all the folate forms tested (folic acid, formyltetrahydro- folate, and methyltetrahydrofolate), while I T IS NOW CLEARthat vitamin B,2 deficiency causes a profound dis- turbance of folate metabolism. The finding of high serum folate concentra- tions2 and low erythrocyte folate3 in patients with vitamin B,2 deficiency has led to the well-known hypothesis proposed by Noronha and Silverman4 and Herbert and Zalusky.2 Since vitamin B12 is needed as the coenzyme of homocysteine methyltransferase, it has been suggested that in vitamin B,2 deficiency there is an accumulation of N5- (N5-CH3-THF) which leads to a depletion in cells of the other forms of folate that are active in nucleic acid synthesis. The validity of the methylfolate trap has been questioned.5 � However, many of the distur- bances of folate metabolism found in vitamin B,2 deficiency can be explained by the trap hypothesis.8'9 The accumulation of N5-CH3-THF in cobalamin de- ficiency'#{176} and the effect of methionine in preventing the irreversible formation of methyltetrahydrofolate are consistent with the theory. Other disturbances of folate metabolism in vitamin B,2 deficiency, such as decreased transport of N5-CH3-THF into cells'2 4 and decreased content and synthesis of intracellular pteroylpolyglutamates,'5�'8 do not exclude the methylfolate trap. Deranged DNA synthesis in vitamin B,2 deficiency has been shown by de- fective suppression of the incorporation of tritiated thymidme (3H-TdR) into