STUDIES ON THE BIOCHEMICAL DEFECT OF PERNICIOUS ANEMIA. I. IN VITRO OBSERVATIONS ON OXYGEN CONSUMPTION, HEME SYNTHESIS AND DEOXYRIBONUCLEIC ACID SYNTHESIS BY PERNICIOUS ANEMIA BONE MARROW12

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Abstract
Pernicious anemia bone marrow was incubated in vitro for periods of 5-10 hours. The incorporation of glycine-2-C14 into heme and of formate-C14 into deoxyribonucleic acid was measured. It was observed that vitamin B12 in concentrations of 0.001 to 0.1 [mu]g/ml accelerated the rate of DNA synthesis, but did not affect oxygen consumption or heme synthesis. In some experiments, folic acid also accelerated DNA synthesis. Using the liquid suspension-vaccine vial culture technique, it was observed that the ability of marrow cells to synthesize DNA was markedly reduced after 24 hours and had virtually ceased at 48 hours. It was concluded that the suspension culture-technique is not a suitable method for studies of DNA synthesis by marrow. Additional observations comparing DNA synthesis by marrow cells in normal serum with that in pernicious anemia serum failed to demonstrate any evidence of an inhibitor of DNA synthesis in pernicious anemia serum.