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Bone marrow cells from vitamin B12- and folate-deficient patients
misincorporate uracil into DNA
SN Wickramasinghe and S Fida
Department of Haematology, St Mary's Hospital Medical School, Imperial
College of Science, Technology & Medicine, London, UK.
Bone marrow cells from 15 patients with normal deoxyuridine (dU)
suppression test results, 3 healthy subjects, and 11 patients with
megaloblastic anemia caused by vitamin B12 or folate deficiency were
examined for misincorporation of uracil into DNA. Cells were incubated with
[5-3H] uridine for 2 hours and their DNA extracted. The DNA was hydrolyzed
to deoxyribonucleosides with DNase 1, phosphodiesterase and alkaline
phosphatase, and any dU present was separated from other
deoxyribonucleosides by Aminex A6 chromatography. The quantity of dU/mg DNA
and the radioactivity in the dU peak/mg DNA were then calculated. The
results clearly showed that there was markedly increased uracil
misincorporation into the DNA of vitamin B12- or folate-deficient marrow
cells. Misincorporation of uracil into DNA may be an important biochemical
lesion underlying both the megaloblastic change and the ineffectiveness of
hematopoiesis in vitamin B12 and folate deficiency.
Volume 83,
Issue 6,
pp. 1656-1661,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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