Proliferation of Megaloblasts in Pernicious Anemia as Observed from Nucleic Acid Metabolism

In order to elucidate the nature of the megaloblastic lesion at the cellular level, DNA, RNA, and protein synthesis was studied in megaloblasts of pernicious anemia. While microphotometric estimation of DNA content showed an increase in cells with DNA values ranging around the 4c value, autoradiographic studies with H³-thymidine indicated, rather, a decreased ability to synthesize DNA. Combined microphotometric and autoradiographic studies suggested the impaired DNA synthesis with occasional arrests of synthesis, as well as the prolongation of the S period with or without the prolongation of the G2 period. On the other hand, active incorporation of H³-uridine and H³-leucine indicated active or unaffected RNA and protein synthesis. Vitamin B₁₂ treatment rapidly corrected these aberrant patterns of synthesis. The significance of these findings has been discussed in relation to the mechanism of megaloblastic hemopoiesis.