Chromosomal studies were performed in phytohaemagglutinin-stimulated cultures of lymphocytes and in bone marrow cells without culture from 115 patients with megaloblastic anaemia resulting from nutritional deficiency of folate and vitamin B12 Essentially similar chromosomal abnormalities were observed in the two cell lines. These were characterized by striking morphological aberrations such as elongation and despiralization (uncoiling or incomplete contraction), increased frequency of chromosome breakage and centromere spreading. Numerical abnormalities, chromatid exchanges and translocations were virtually absent. Autoradiographic studies of chromosomes after pulse-labelling with 3H-thymidine during the terminal 6 h of phytohaemagglutinin-stimulated lymphocyte cultures revealed a differential pattern of distribution of the radionucleotide in the chromosomes of megaloblastic lymphocytes as compared to those from normal lymphocytes. Repeated chromosomal studies were done in 65 of these patients at various intervals after starting therapy with the deficient vitamins. After 48 h of therapy, chromosomal abnormalities were remarkably reduced in the bone marrow; but many of these morphological chromosomal changes (i.e. despiralization and breaks) persisted in the lymphocytes of a significant proportion of patients for variable periods up to 6–12 months after haematological remission resulting from therapy with the deficient vitamins. These abnormalities did not, however, persist after remission in those patients who had repeated episodes of infections.

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