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• W2034222878 endingPage "592" @default.
• W2034222878 startingPage "575" @default.
• W2034222878 abstract "Summary. The synthesis of thymine DNA from deoxyuridine and uridine was studied by culturing human bone marrow for 1–3 hours in the presence of radioactive-labelled nucleosides. In the current study, this in vitro system appeared useful to test the potential efficacy of agents (such as methionine) which might be used to improve or retard improvement of patients with megaloblastic anaemia. In the bone marrow from patients with B12-deficient or folate-deficient megaloblastic anaemia, there was defective incorporation of deoxyuridine into thymine DNA. This defect was partially corrected by added B12 in the B12-deficient but not the folate-deficient marrows, and completely corrected by folic acid (pteroylglutainic acid) in both types of deficient marrow. The folate antagonist rnethotrexate blocked the corrective effect of B12. Incorporation of labelled uridine into DNA of B12-deficient megaloblastic marrow was enhanced less by B12 than by PGA. Vitamin B12 antagonists failed to depress the incorporation of labelled uridine into DNA in bone marrows from both normal and B12-deficient patients. These results support the concept that inadequate DNA synthesis in B12 deficiency is due in large measure to blockade in folate metabolism brought about by lack of B12. 5-Methyl-tetrahydrofolate, which may accumulate in B12 deficiency, failed to correct the defect in DNA synthesis, adding further evidence to the concept of metabolic trapping of this form of folate in B12 deficiency. Thus, riboside reduction in man may be independent of B12, as it is in E. coli, rather than dependent on B12, as it is in L. leichmannii." @default.
• W2034222878 created "2016-06-24" @default.
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• W2034222878 date "1968-06-01" @default.
• W2034222878 modified "2023-10-16" @default.
• W2034222878 title "Deranged DNA Synthesis by Bone Marrow from Vitamin B₁₂-Deficient Humans" @default.
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• W2034222878 doi "https://doi.org/10.1111/j.1365-2141.1968.tb00364.x" @default.
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