Deoxyuridine suppression: Biochemical basis and diagnostic applications

Abstract

The deoxyuridine (dU) suppression test evolved out of investigations into the biochemical basis of the megaloblastic changes seen in vitamin B 12 and folate deficiency. Although the abnormality in dU suppression which occurs in vitamin B 12- or folate-deficient states is assumed to reflect impaired methylation of deoxyuridylate, there is still no direct demonstration that this is so. Furthermore, there is evidence that reactions other than the methylation of deoxyuridylate are involved in the phenomenon of dU suppression. Nevertheless, in clinical practice abnormal dU suppression serves as a sensitive index of the presence of megaloblastosis due to vitamin B 12 or folate deficiency. dU suppression is also abnormal in a number of conditions other than vitamin B 12 or folate deficiency, but its overall specificity in detecting tissue dysfunction due to these two deficiency states is considerably higher than that of the serum vitamin B 12 or red cell folate levels. Consequently, the test enables us simply and rapidly to define those patients in whom macrocytosis is unrelated to a deficiency of vitamin B 12 or folate. For these reasons, the dU suppression test has been adopted by several laboratories across the world for investigating patients with (a) possible vitamin B 12 or folate deficiency, (b) macrocytosis, and (c) megaloblastic erythropoiesis. Since the dU suppression test is abnormal in transcobalamin II deficiency and in some congenital disorders of vitamin B 12 and folate metabolism, it is very useful in the investigation of obscure anaemias in infancy and childhood. In addition, it has contributed to our understanding of the mechanisms underlying the myelotoxicity of certain drugs, and particularly of nitrous oxide.