Cytogenetic and Cytochemical Studies on Marrow Cells in B12 and Folate Deficiency

Menzies, Rosa C.; Crossen, Peter E.; Fitzgerald, P. H.; Gunz, F. W.

doi:10.1182/blood.v28.4.581.581

Cited by 92 publications

(12 citation statements)

References 18 publications

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“…In fact, with the exception of Case 5, who had the highest pre-treatment folatc level in this study, it appeared that the folate therapy further diminished the proportion of earlypolychromatic cells in DNA synthesis (Table IV). Since megaloblastic erythropoiesis due to folate deficiency is known to be associated with an arrest in DNA synthesis (Menzies et al, 1966), a possible explanation for this finding might be that folate deficiency is associated with some degree of depression in the rate ofDNA synthesis, and that this is accelerated by folate therapy.…”

Section: Discussionmentioning

confidence: 99%

“…This paper describes the results of a study of erythroblast proliferation in P-thalassaemia, using a combination of quantitative cytochemistry and autoradiography. The value of this technique in the detection of disturbances in cell proliferation has been established in previous studies of pernicious anaemia and sideroblastic anaemia (Menzies ct al, 1966;Bock et al, 1967;Yoshida et a/, 1968;Wickramasinghe et al, 1968a Wickramasinghe et al, , b, 1969.…”

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confidence: 95%

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Proliferation of Erythroblasts in Beta‐Thalassaemia

et al. 1970

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Erythropoiesis has been studied by the technique of combined Feulgen microspectrophotometry and 3H-TdR autoradiography in nine children with Pthalassaemia. A major kinetic aberration was demonstrated in the early polychromatic erythroblasts, which showed an accumulation in G, and a marked decrease in the proportion of cells in DNA synthesis, indicating an arrest of proliferation in these cells. In scven of the cases studied there was also an increased frequency of G, cells relative to the small number in DNA synthesis, suggesting a failure to enter mitosis.The death of these arrested cells could account for the ineffectiveness of erythropoiesis in this disease. Low serum folate levels were found in all the patients who were not already on folate therapy, but the disturbance in cell proliferation persisted after the administration of folic acid.Ferrokinctic and porphyrin excretion studies have shown that ineffective erythropoiesis is an important factor in the pathogenesis of the anaemia in P-thalassaemia (Sturgeon & Finch, 1957; Grinstein ct al, 1960;Malamos et al, 1961) and indicate that, in addition to the impairment of P-chain synthesis, there must also be a disorder of erythroblast proliferation in this disease. This paper describes the results of a study of erythroblast proliferation in P-thalassaemia, using a combination of quantitative cytochemistry and autoradiography. The value of this technique in the detection of disturbances in cell proliferation has been established in previous studies of pernicious anaemia and sideroblastic anaemia (Menzies ct al, 1966;Bock et al, 1967;Yoshida et a/, 1968;Wickramasinghe et al, 1968a Wickramasinghe et al, , b, 1969. MATERIAL A N D METHODSPatients. Eight patients with 8-thalassaemia major and one patient with homozygous thalassaemia intermedia (Case 9) have been studied; these children were either Greek or Turkish Cypriots resident in London. The pertinent haematological data at the time of the initial bone-marrow analysis are summarized in Table I. Apart from Case 9, who was receiving regular folate therapy, all patients had serum folate levels below the normal range. In six of these patients, the investigation was repeated following the oral administration of folic acid, 13 mg daily for at least 6 weeks.Cell cycle distribution. The method used for the determination of the distribution of erythroblasts in interphase-G,, S, G,, and U-was a modification of that described previously (Wickramasinghe et al, 1968a). GI represents post-mitotic cells with a diploid (2. ) DNA 719

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Section: Discussionmentioning

confidence: 99%

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confidence: 95%

Proliferation of Erythroblasts in Beta‐Thalassaemia

et al. 1970

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“…Folate deficiency during this critical period might then promote genetic damage. Folic acid deficiency has been associated with an increased frequency of chromosomal breaks, gaps, triradial and quadriradial forms, ring chromosomes, and despiralization in vitamin deficient patients and in human lymphocytes and CHO cells grown in low folate medium [Heath, 1966;Menzies, 1966;Das et al, 1986;Li et al, 1986;Chen et al, 1989;Libbus et al, 1990). These chromosome aberrations, except for the despiralization, resemble the chromosome damage caused by nucleotide precursor pool imbalances in cultured cells [Kunz, 1982;Meuth, 19841.…”

Section: Studies Of Nutritional Factorsmentioning

confidence: 99%

Factors influencing mutation at the hprt locus in T‐lymphocytes: Studies in normal women and women with benign and malignant breast masses

Branda

O’Neill

Jacobson‐Kram³

et al. 1992

Environ and Mol Mutagen

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A prospective, longitudinal study was performed to test the hypothesis that environmental factors (e.g., diet or cigarette smoking) modulate genetic damage caused by treatment for breast cancer and render these women more susceptible to developing second malignancies. A total of 107 women (49 with breast cancer, 52 with benign breast masses, and 6 normal women) were enrolled. This report describes initial studies at the time of enrollment and disease presentation. Mutant frequency at the hprt locus and cloning efficiency of peripheral blood lymphocytes did not differ significantly among the 3 groups. Mutant frequency increased with age, with a history of cigarette smoking, and with the number of years that current smokers used cigarettes. There was no correlation in women with benign masses between mutant frequency and the incidence of chromosome aberrations (28 women) or sister chromatid exchanges (23 women). A maternal history of breast cancer did not influence mutant frequency. There was no significant relationship between dietary intake of vitamins A, B12, C and E, folacin, selenium, calcium, caffeine, or multivitamin pills, and mutant frequency. Serum folate levels in the deficient range were associated (P = 0.02) with elevated mutant frequencies, whereas SCE rates inversely correlated with serum vitamin B12 levels. These results confirm the importance of age and, less so, cigarette smoking as factors that influence mutant frequency and suggest that a micronutrient, folic acid, may modify genetic damage at the hprt locus. To the extent that somatic mutation contributes to carcinogenesis, these environmental factors may enhance the risk of developing malignant transformation.

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“…In the erythroblastic cell compartment of PA, studies have shown an increased number of cells with DNA values ranging around the 4c level and several cells with DNA values between 2c and 4c values, which did not participate in DNA synthesis as judged by ['HITdR labelling (Menzies et al, 1966; Wickramasinghe et a!, 1968;Yoshida et al, 1968). In our three cases of PA, besides the macrocytic anaemia there was also a striking thrombocytopenia (platelet counts of 40 000-60 ooo/pl).…”

Section: Pernicious Anaemiamentioning

confidence: 99%

Polyploidization of Megakaryocytes in Normal Humans, in Patients with Idiopathic Thrombocytopenia and with Pernicious Anaemia

1971

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Summary. Polyploidization of human megakaryocytes was studied in bone marrow aspirates from three normal individuals, three patients with idiopathic thrombocytopenic purpura (ITP) and three patients with pernicious anaemia (PA). The cells were labelled in vitro with tritiated thymidine and analysed by a combined cytophotometric and autoradiographic method. Cells were divided into types I, II and III. Normal megakaryocytes showed ploidy stages from 4c to 32c, the 4c stage occurring only in type I. The labelling indices showed that in normal megakaryocytes polyploidization takes place in type I and II and not in type III cells. This study provided evidence for alternation of DNA synthesis and rest periods. It is postulated that rhythmical polyploidization in megakaryocytopoiesis takes place. The progressive increase in the proportion of cells in successive resting periods (G‐phases) suggests that high ploidy cells have longer resting periods than low ploidy cells. In ITP, megakaryocyte morphology, labelling indices and distribution of DNA content were normal. Assuming a normal ploidy composition in ITP, the megakaryocytic hyperplasia observed in typical cases may be explained by an increased influx from the unrecognizable progenitor cell. In PA, an arrest of megakaryocytic DNA synthesis was observed comparable to that found in megaloblastic erythropoiesis.

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Cytogenetic and Cytochemical Studies on Marrow Cells in B12 and Folate Deficiency

Cited by 92 publications

References 18 publications

Proliferation of Erythroblasts in Beta‐Thalassaemia

Proliferation of Erythroblasts in Beta‐Thalassaemia

Factors influencing mutation at the hprt locus in T‐lymphocytes: Studies in normal women and women with benign and malignant breast masses

Polyploidization of Megakaryocytes in Normal Humans, in Patients with Idiopathic Thrombocytopenia and with Pernicious Anaemia

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