[Evaluation of Ag-positive chromosomal nucleolus organizer regions in malignant cell interphase].
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Biomedical subjects
Publications and source records attributed to V M Pogorelov.
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Computer morphometry revealed statistically significant (P less than 0.001) decrease in the number and area of nucleoli and ribosomal gene activities (as demonstrated by AgNOR staining) in primary mouse embryonal fibroblast cultures infected by oncogenic adenovirus SA7(C8). Even more drastic increased in these parameters was found when serum-depleted cultures were infected. There were no effects on nucleolar and AgNOR parameters in mock-infected cultures. It is suggested that an increase in the ribosomal gene activity may reflect synthesis of SA7(C8) early gene products in target cells.
The Ag-staining intensity of interphase bone marrow granulopoietic cells decreases during their maturation as evidenced by TV computerized morphometry. These data are in accordance with the phenomenon of RNA transcription reduction in mature granulocytes. The Ag-positive material amount increases during S and G2 phases of proliferative pool granulocytes. 8 days after every day injection of 20 mg/kg cyclophosphamide an integral area of silver grains in proliferative pool granulocytes decreased 1.5 times. In mature granulocytes it decreased and was two times higher than in the control. The nuclear area of all granulocytes increased. There was a positive correlation (p less than 0.01) between the quantity of the silver grains and nuclear areas. It seems that mature granulocytes inherit the increased Ag-positive material amount from G2 blocked progenitors (promyelocytes and myelocytes) and this increase is not due to the RNA transcriptional activity.
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Daily injection of cyclophosphamide (20 mg/kg body weight) for 7 days resulted in accumulation of 50% of rat bone marrow granulocytes in G2. Tetraploid neutrophils were hypersegmented (7.25 +/- 0.33) in comparison with diploid ones (3.92 +/- 0.33). After 14 days of cyclophosphamide treatment tetraploid hypersegmented neutrophils could be found in peripheral blood. Diploid neutrophils in these animals were also hypersegmented (4.78 +/- 0.14 versus 3.15 +/- 0.02 in control, p less than 0.001). Nucleolar ribosomal gene activities, evaluated by morphometry of silver nucleolar grains, decreased on bone marrow granulocytes in the course of differentiation in control rats. After cyclophosphamide treatment mature granulocytes contained more silver grains than in controls which may be explained by conservation of silver binding sites of nucleoli from the stages of promyelocytes and myelocytes. These results suggest two mechanisms of hypersegmented neutrophil, generation in cyclophosphamide treated rats: the first, via maturation of myelocytes arrested in G2, and second, a direct one, without tetraploid granulocyte involvement.
Interphase lymphoid nucleoli of Ag-NOR stained site areas were measured on the TAS system in peripheral blood lymphoid cells with the known immunologic phenotype of 19 patients with lymphoid neoplasia (non-Hidgkin's lymphoma, CLL, hair-cell leukemia) and 10 healthy donors. The area of Ag-granules in neoplastic cells is much greater than in normal lymphocytes and does not correlate with a proliferation of cells but correlates with a malignancy grade of the disease. These data are discussed in terms of rDNA transcription patterns in malignant cells.
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The examination of peripheral blood lymphocytes from persons exposed to low-dose radiation after the Chernobyl accident demonstrated that the exposure to radiation at the time of the accident and further living in the contaminated territory entail a significant increase in the number of cells with a large thick nucleus and scare cytoplasm. Such morphological picture may be attributed to stable adaptation typical for persistent activation of the general adaptation syndrome and is explained by adaptation-stress relations.
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The effects of cis- and trans-isomers of atypical neuroleptic carbidine on the synthesis of dopamine and its autoreceptor regulation in the striatum and nucleus accumbens of rats were examined by blocking decarboxylase of L-aromatic amino acids and interrupting the nerve impulse flow in the dopaminergic neurons. The striatal release and metabolism of dopamine were studied in vitro by employing K(+)-stimulated efflux from isolated striata and in vivo by the microdialysis in freely moving rats. Carbidine trans-isomer, unlike its cis-isomer, was shown to enhance the biosynthesis of dopamine via blockade of presynaptic autoreceptors presumably located on the dopaminergic terminals. The trans-isomer was found to be much more potent by affecting the neurochemical parameters of dopaminergic neurotransmission, which are essential for the drug to produce its antipsychotic effect.
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In search for markers of tumor cell resistance to cytostatic drugs, cytologic characteristics were compared of resistant and sensitive to rubomycin variants of mouse P-388 leukemia. Morphocytochemical, morphometrical and cytogenetic investigations were performed as well as measurements of intracellular pH. As shown by the fluorescent test, pH levels in rubomycin-sensitive and resistant subpopulations differed. This fact evidences an important role of intracellular pH in inducing the resistance and revealed some mechanisms of rubomycin-resistant tumor cell selection.
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