Results of Three Years’ Experience with the Deoxyuridine Suppression Test

Abstract

The results of deoxyuridine (dU) suppression tests performed on 400 marrow samples aspirated over a 3-year period are summarised. High dU-suppressed values were found in all patients with vitamin B₁₂ or folate deficiency, in some patients receiving inhibitors of dihydrofolate reductase, in 4 of 19 epileptics receiving anticonvulsants and in 2 of 21 patients with iron deficiency anaemia. High dU-suppressed values were found even in those vitamin B₁₂- or folate-deficient patients who had serum vitamin B₁₂ and red cell folate levels within the normal range. Conversely, some patients with subnormal serum vitamin B₁₂ levels (including 1 on high doses of penicillin, 1 on anticonvulsant therapy and 2 vegans) and some patients with subnormal red cell folate levels gave normal dU-suppressed values, and were considered not to suffer from the metabolic consequences of vitamin B₁₂ or folate deficiency. All of the patients with megaloblastic erythropoiesis induced by the anti-purine drugs or cyclophosphamide, 4 patients with megaloblastic erythropoiesis associated with primary acquired sideroblastic anaemia, a chronic myeloproliferative disorder or subacute erythraemic myelosis and a proportion of the patients with megaloblastic erythropoiesis associated with anticonvulsant therapy, chronic alcoholism, acute myeloid leukaemia or myelomatosis also gave normal dU-suppressed values. The addition of 1 μg cyanocobalamin per millilitre of marrow culture together with the deoxyuridine caused a significant reduction in the dU-suppressed value in 86% of vitamin B₁₂-deficient patients and the addition of 10 μg pteroylglutamic acid per millilitre of marrow culture caused a significant reduction in 91% of folate-deficient and 57% of vitamin B₁₂-deficient patients.

Correlations between holo-transcobalamin II, holo-haptocorrin, and total B12 in serum samples from healthy subjects and patients.

“…As in the case of total serum B1,,' holo-hapto-A, 8 corrin and holo-TCII concentrations had a log-normal distribution. Therefore, the data A} !…”

Biochemical mechanisms in the Killmann experiment: critique of the deoxyuridine suppression test.

“…This experiment in one or another modification has been widely used and has been recommended as a routine clinical test for cobalamin or folate deficiency (17,22,23 [8-3H]deoxyadenosine (14.4 Ci/mmol), [8-3H]deoxvguanosine (6.5 Ci/mmol), and [5-3H] Thvmidine kinase was assaved byv imeasuiremiienit ofthe phosphorvlation ofradioactive thymidine to thymiidine phosphates, which are then bouncl to DEAE-cellulose paper (28,29 50-,ul aliquots of the reaction mixture were applied to DEAEcellulose paper disks, which were promptly immersed into 1 mM ammonium formate (20 ml/disk); residual thymidine was eluted from disks by washing twice for 10 min in 1 mM ammonium formate, once in water, and once in 95% ethanol for 5 min, respectively. Disks were dried for 10 min in counting vials by infrared lamp, cooled and assayed for radioactivity in 10 ml of Aquasol.…”

Derangement of DNA Synthesis in Erythroleukaemia. Normal Deoxyuridine Suppression and Impaired Thymidine Incorporation in Bone Marrow Culture

“…Normal dU suppression values in ery throleukaemia bone marrows were very briefly reported by Waxman and Herbert [25] in 6 patients and by Wickramasinghe and Saunders [28] in 2 patients without providing any data on 3H-TdR incorpora tion by the marrow cells. The present data further showed that in contrast to vitamin B12 and folate-deficient bone marrow, in which 3H-TdR incorporation into DNA of erythroblasts was higher than normal, the incorporation of this radionucleoside in bone marrow of patients with erythroleu kaemia was significantly lower than in nor mal bone marrows.…”