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The Effect of Deoxyuridine, Vitamin B 12 , Folate and Alcohol on the Uptake of Thymidine and on the Deoxynucleoside Triphosphate Concentrations in Normal and Megaloblastic Cells
Author(s) -
Ganeshaguru K.,
Hoffbrand A.V.
Publication year - 1978
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1978.tb03636.x
Subject(s) - deoxyuridine , folinic acid , pernicious anaemia , vitamin b12 , microgram , medicine , thymidine , bone marrow , endocrinology , chemistry , vitamin , dihydrofolate reductase , megaloblastic anemia , phytohaemagglutinin , biochemistry , lymphocyte , methotrexate , in vitro , chemotherapy , fluorouracil , dna
SUMMARY 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 ro.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 B 12 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 μg/ml. Vitamin B 12 (100 μug/ml) only corrected the test in vitamin B 12 deficiency and 5‐methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 μg/ml. Among 16 patients with subnormal serum levels of both vitamin B 12 and folate, vitamin B 12 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 pliytohaemagglutinin 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 B 12 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.