Effect of folate and cobalamin compounds on the deoxyuridine suppression test in vitamin B12 and folate deficiency.

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, macrocytosis, 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, formyltetrahydrofolate, and methyltetrahydrofolate), while the various cobalamins, cyano-, hydroxo-, methyl-, and deoxyadenosyl cobalamin, failed to correct the abnormality. In vitamm B,2 deficiency, methyltetrahydrofolate had little or no effect, folic acid had a partial effect, and formyltetrahydrofolate almost totally corrected the defect. The defective blocking effect of dU was very poorly corrected by deoxyadenosylcobalamin, partially corrected by cyanocobalamin, and corrected far better by hydroxoor methylcobalamin. The test became normalin vitamin B,2 deficiency only when both methylor hydroxocobalamm and methyltetrahydrofolate were added in vitro. These results provide further evidence in favor of the “methylfolate trap” hypothesis as the explanation for the defect in DNA synthesis in vitamin B,2 deficiency.