The effect of deoxyuridine, vitamin B12, folate and alcohol on the uptake of thymidine and on the deoxynucleoside triphosphate concentrations in normal and megaloblastic cells.
Deoxyuridine suppression of labelled thymidine uptake tests were performed in the bone marrows of 58 patients with megaloblastic anaemia (haemoglobin less than 10.0 g/dl) and invariably gave values (range 10.3-58.8%) above the range in 16 control marrows (range 1.0-9.0%). Folinic acid corrected the test equally well in either folate or vitamin B12 deficiency, even at concentrations as low as 60 ng/ml. Folic acid also corrected the test equally well in either deficiency but was only effective at concentrations down to 5 microgram/ml. Vitamin B12 (100 microgram/ml) only corrected the test in vitamin B12 deficiency and 5-methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 microgram/ml. Among 16 patients with subnormal serum levels of both vitamin B12 and folate, vitamin B12 partially corrected the test in eight, including all five with pernicious anaemia, but had no effect in the other eight. Despite the clear-cut results of the dU suppression test, measurement of the deoxythymidine triphosphate (dTTP) concentration in normal and megaloblastic phytohaemagglutinin stimulated lymphocyte cultures or short-term bone marrow cultures gave no clear-cut differences between normal and megaloblastic cells after addition of deoxyuridine nor did the addition of vitamin B12, folic acid or folinic acid either alone or with deoxyuridine produce consistent changes in the dTTP concentration in lymphocytes or bone marrow cells in megaloblastic anaemia. Alcohol caused a rise in deoxyadenosine triphosphate concentration in normal PHA-stimulated lymphocytes which was concentration dependent but caused no consistent change in any of the other three deoxynucleoside triphosphate (dNTP) concentrations. Diphenylhydantoin (10(-3)M, 10(-4)M) had no consistent effect on any of the four dNTP concentrations.
D000748:Anemia, Macrocytic / Q000378:metabolism*; D000749:Anemia, Megaloblastic / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism*; D003857:Deoxyuridine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D013763:Tetrahydrofolates / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013942:Thymine Nucleotides / Q000378:metabolism*; D014805:Vitamin B 12 / Q000494:pharmacology
D003838:Deoxyadenine Nucleotides; D013763:Tetrahydrofolates; D013942:Thymine Nucleotides; D000431:Ethanol; D004247:DNA; D005492:Folic Acid; D014805:Vitamin B 12; D002955:Leucovorin; D013936:Thymidine; D003857:Deoxyuridine