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Thymidylate concentration in megaloblastic anaemia

Abstract

MEGALOBLASTIC anaemia is thought to be caused by a disturbance of DNA synthesis in the bone marrow. The most common causes are deficiencies of folate or vitamin B12 which are thought to interfere directly or indirectly with supply of thymidine triphosphate (dTTP, thymidylate) one of the four immediate precursors of DNA1,2 (Fig. 1). We have previously shown that acute folate deficiency caused by the antifolate drug, methotrexate, does indeed cause a fall in the intracellular concentration of dTTP3. The present paper reports studies of the cellular concentration of dTTP and of the other three deoxyribonucleotide precursors of DNA, deoxyadenosine triphosphate (dATP), deoxyguanosine triphosphate (dGTP) and deoxycytidine triphosphate (dCTP) in the bone marrow cells and phytohaemagglutinin (PHA)-stimulated lymphocytes from patients with untreated megaloblastic anaemia due to vitamin B12 or folate deficiency. Surprisingly, no reduction in dTTP concentration was found in either cell.

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HOFFBRAND, A., GANESHAGURU, K., LAVOIE, A. et al. Thymidylate concentration in megaloblastic anaemia. Nature 248, 602–604 (1974). https://doi.org/10.1038/248602a0

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