Cytogenetic studies on MIC gas-exposed persons in Bhopal.
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Accidents, Occupational↗
Biomedical subjects
B C Das
Publications and source records attributed to B C Das.
Cytogenetic studies in leprosy patients before and after chemotherapy.
The frequencies of chromosome aberrations and sister chromatid exchanges (SCEs), cell proliferation kinetics and mitotic indices were studied in peripheral blood lymphocyte cultures of leprosy patients both before and after chemotherapy. The differences in the frequencies of chromosome aberrations and SCEs between controls, paucibacillary and multibacillary patients were found to be statistically highly significant (P less than 0.001). The extent of cytogenetic damage seemed to depend on the severity of the disease. Lymphocytes of untreated leprosy patients showed a low mitotic index and a slow rate of cell proliferation. Following combined treatment with dapsone and rifampicin there was an increase, but to a lesser degree (P less than 0.01), in the frequency of SCEs and chromosome aberrations while the drug combination of dapsone, rifampicin and clofazamine had a nonmutagenic effect on chromosomes of the patient. Furthermore, after drug treatment, the cell proliferation rate and mitotic indices in paucibacillary patients were comparable to that of controls. These results indicate the clastogenic potency of Mycobacterium leprae and the remedial effects that follow therapeutic drug treatment.
Adult↗
Differential sensitivity of peripheral blood lymphocytes of untreated leprosy patients to mitomycin C.
The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 microgram/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant (p less than 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 +/- 1.19 in controls, 19.97 +/- 3.51 in PB, and 29.66 +/- 5.92 in MB patients. The differences in the frequency of MMC-induced SCEs between the 3 groups were found to be highly significant (p less than 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease.
Cells, Cultured↗
Risk factors related to biological behaviour of precancerous lesions of the uterine cervix.
In a study of factors related to cervical carcinogenesis, a cohort of 1,107 cervical dysplasia along with 1,077 controls matched for age and parity were followed up prospectively. During the follow up 75 dysplasia cases progressed to carcinoma in situ. The overall rate of progression of dysplasia to malignancy was observed to be 15.7% at the end of 108 months of follow-up. The analysis of progression rates in relation to various factors revealed significantly higher progression rates for initially higher grade of dysplastic lesions, and early age at consummation of marriage (ACM). The other factors, such as religion, literacy status of the patient, number of pregnancies, presence of cervical erosion, history of fetal loss and positivity to HSV-II antibodies, did not reveal statistical significance. The case-control comparison for detection of HPV 16/18 by in situ hybridisation revealed the presence of HPV 16/18 sequences in 67.3% of the dysplasia subjects progressed to carcinoma in situ while 27.3% of precancerous cases regressed to normalcy. The difference was found to be statistically significant (P less than 0.001).
Adult↗
Environmental sanitation in an urban field area: a report.
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Demography↗
Effects of lepromatous leprosy (LL) serum factor(s) on normal blood lymphocytes.
To investigate the clastogenic activity of sera from leprosy patients, normal peripheral blood lymphocytes were cultured in both inactivated and noninactivated lepromatous leprosy (LL) sera. An increase in the frequency of chromosome aberrations was observed in normal lymphocyte cultures supplemented with both inactivated (5.2%) and noninactivated (5.0%) LL serum compared to that of cultures supplemented with normal human AB+ serum (2.4%). An enhanced frequency of sister chromatid exchanges (SCEs) was also observed in normal lymphocyte cultures supplemented with both inactivated (8.2 +/- 3.85) (mean +/- S.D.) and noninactivated (8.3 +/- 4.61) LL serum compared to that of controls (6.8 +/- 3.45). The normal blood lymphocyte cultures with LL serum have revealed a slow cell-cycle kinetics at a 48-hr incubation period, but a slightly faster proliferation rate was observed at 72 hr compared to cultures supplemented with normal human AB+ serum, indicating a depressive effect of LL serum on normal blood lymphocyte proliferation. The results obtained from the inactivated LL serum showed that the factor(s) which induce chromosomal damage, depress the mitotic index and the cell proliferation rate were not destroyed at 56 degrees C. These results are the first documentation of cytogenetic effects of LL sera on normal human peripheral blood lymphocytes.
Adult↗
Human papillomavirus and cervical cancer in Indian women.
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Adolescent↗
Variation in spontaneous chromosomal damage as a function of biologic rhythms in women.
An unequivocal observation of a higher rate of cellular genetic damage in terms of increased frequencies of sister chromatid exchanges (SCEs) and chromosome aberrations during "ovulatory" and "estrogenic" stages as compared with those of "progestogenic" stage of the menstrual cycle in women and the reported fluctuations in SCEs as a function of time in men indicate that chronobiologic considerations are essential in the design of studies of humans and animals experiments. It seems that female subjects are more influenced by biologic rhythms because of specific hormonal cycles and are sensitive to genetic damage during ovulatory/estrogenic stages of the menstrual cycle.
Adult↗
Chromosomal phenotypes in patients with precancerous lesions of the uterine cervix progressed to cancer during follow-up.
A cytogenetical analysis of chromosomal aberrations, sister chromatid exchanges (SCEs), C-band heteromorphisms and nucleolar organizer regions was done in lymphocytes of 30 patients with precancerous lesions of the uterine cervix progressed to carcinoma and of 30 patients with nonprogressed lesions in a period of 60 months follow-up, in order to identify if any differences existed between low-risk and high-risk dysplasias. Increased frequency of chromosomal breaks, SCEs and C-band heteromorphisms of chromosome 1 and decreased activity of ribosomal genes was observed in patients with dysplasias progressed to carcinoma compared to that of nonprogressed precancerous lesions. The present study thus suggests an intimate relationship between the constitutional chromosomal phenotypes and development of cancer, and these may serve as useful biological markers in defining dysplasias at high risk to progress to cancer.
Adult↗
Factors that influence formation of sister chromatid exchanges in human blood lymphocytes.
Sister chromatid exchange (SCE) reflects an interchange of DNA sequences between helices in a replicating chromosome. This was initially accomplished by Taylor and colleagues (1957) using tritiated thymidine incorporation followed by autoradiography. The development of an elegant technique for differential staining of sister chromatids by incorporating a thymidine analog, 5-bromodeoxyuridine (BrdU) has greatly simplified the detection of SCEs in metaphase chromosomes. In recent years, the analysis of SCE has been considered to be a highly sensitive and additional (i.e., with chromosome aberrations) end point for measuring mutagenic/carcinogenic potential of various environmental agents and is increasingly being used to detect and differentiate among chromosome fragility human diseases that predispose to neoplasia. Attention has been focused to see if the induction of SCEs in lymphocyte cultures can be used as a reliable "biological dosimeter" for genetic risk assessment and to monitor the exposed populations. Several physical or preparatory as well as biological factors that modify the response and formation of SCEs make the monitoring difficult. The purpose of this article is to review and analyze these factors to facilitate an effective development of a standard protocol for SCE testing and for appropriate evaluation of test results. This may also provide clues to understand the yet unknown molecular mechanism(s) and biological significance of SCE formation.
Humans↗
Chromosome abnormalities in referred patients--a five year study.
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Chromosome Aberrations↗
The fate of X-ray-induced chromosome aberrations in blood lymphocyte culture.
The BrdU-Giemsa method which facilitates an unequivocal identification of metaphases at different cycles has been utilized to investigate the fate of X-ray-induced chromosome aberrations in the blood lymphocyte culture system of the Indian muntjac which has the lowest diploid number (2n = 6 female/7 male) and easily distinguishable large-sized chromosomes. The results demonstrate that about 50% of dicentrics and only 12% of rings were transmitted from the first cycle to the second. There were as high as 73% abnormal cells in the second cycle as against 94% in the first cycle following 4.0 Gy. However, the frequencies of dicentrics, rings and of abnormal cells were greatly reduced in the third+ cycles. The frequencies of acentric fragments per post-irradiated first, second and third+ division cell were 2.21, 0.64 and 0.24, respectively. In sharp contrast to all earlier reports, about 75% of them were retained as a single acentric fragment in the second cycle. Analysis of fragment segregation during anaphase separation supports this finding. The survival probability of dicentrics and rings was found to be more than 60% in the second and only 18% in the third+ cycle.
Animals↗
Folate-sensitive fragile sites on the X-chromosome heterochromatin of the Indian mole rat, Nesokia indica.
Folate-sensitive fragile sites have been demonstrated on the X chromosome of the Indian mole rat, Nesokia indica (subfamily Murinae), utilizing peripheral blood lymphocyte cultures. All normal female individuals expressed fragile sites on the constitutive heterochromatic long arm of one of their two X chromosomes (heterozygous expression); in contrast, no fragile sites were found on the single X chromosome of normal males. Preferential transmission of the maternal fragile X to the daughters is therefore suggested. Four sites have been detected so far: fra Xq1, fra Xq2, fra Xq3, and fra Xc (centromeric). It is significant that their location corresponds to the regions where constitutive heterochromatic deletions occur that result in a variety of polymorphic X chromosomes in natural populations of Nesokia. Thus there is a correlation between fragile sites, deletion sites, and karyotypic changes. In individuals that did not reproduce in the laboratory, there were more fragile sites on both X chromosomes of the females (homozygous/double heterozygous expression) and also on the X of the males (hemizygous expression). This difference in fragile site expression from the normal situation could be attributed to one or more new mutations. However, the mechanism by which fragile sites influence reproductive performance is unclear.
Animals↗
Mitomycin C induced chromosomal aberrations and sister chromatid exchanges (SCEs) in lymphocytes of patients with precancerous and cancerous lesions of the uterine cervix.
Baseline and mitomycin C (MMC)-induced chromosomal aberrations and sister chromatid exchanges (SCEs) in blood lymphocytes of patients with cervical precancerous and cancerous lesions and normal women were studied. The baseline frequency of chromosomal aberrations and SCEs revealed a significant increase in higher grades of precancerous (moderate and severe dysplasias) and cancerous lesions compared to those of controls. The MMC-induced chromosomal aberrations and SCEs did not show any differential response in the different groups studied. The results thus indicate that chromosomal instability as observed in precancerous and cancerous lesions is not associated with their sensitivity to mitomycin C.
Chromosome Aberrations↗
Fatal infection with Aeromonas sobria and Plesiomonas shigelloides.
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Adult↗
The number of silver-staining NORs (rDNA) in lymphocytes of newborns and its relationship to human development.
The number of silver-staining NORs (rDNA)/cell and their pattern of distribution were studied in phytohaemagglutinin-stimulated blood lymphocyte chromosomes of different age group individuals starting from newborns to old age (0-75 years) in order to investigate if the number of Ag-NORs or rDNA genes varies during development in humans. The results indicate presence of a relatively high modal number of NORs in newborns and infants (9.00 and 8.00/cell, respectively) and a significantly reduced number in old individuals (6.00/cell) as compared to that of normal adults (7.00/cell). These data are complimentary as well as comparable to the previous findings of Denton et al. (Mech. Ageing Dev., 15 (1981) (1-7). It is suggested that at young age due to an obvious enhanced growth and differentiation more gene sites may be transcriptionally active showing higher number of silver-stained NORs but as the development proceeds and the age advances many of these may be gradually repressed or inactivated.
Adult↗
Co-cultivation of whole blood from male and female muntjacs and the cell proliferation kinetics in vitro.
A mixed blood culture (MBC) of heparinized whole blood from male and female Indian muntjac has been done using the BrdU-Hoechst-sunlight-Giemsa method to study the cell-cycle kinetics in vitro. Blood lymphocytes of both male and female muntjacs show a much shorter cell cycle time, roughly, 10-12 h for the initial but only 8 h for the subsequent cycles. There is a significant difference in the rate of cell proliferation between male and female cells. The male blood cells constitute a majority of the 'slow'-dividing cells which reach a peak at the first cycle of mitosis at 40 h, whereas a similar peak of first cycle mitosis is reached by female cells at 32 h, indicating the occurrence of a high frequency of 'fast' dividing female cells as compared to those of males. This novel sex-based differential cell proliferation kinetics is observed both in mixed and separate cultures. This type of MBC method which is free of interculture variations can be reliably used for comparative studies where two genomes can be distinguished.
Animals↗
Chromosomal damage induced in human lymphocytes by low doses of D-T neutrons.
Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy.
Chromosome Aberrations↗