Biomedical subjects
Publications and source records attributed to V I Platonova.
Chromosome aberrations in donor peripheral blood lymphocyte culture were evaluated before, 14 and 30 days after treatment with a vitamin/mineral complex. Treatment with the complex had no effect on spontaneous level of aberrant cells. The number of chromosome aberrations induced by dioxidine or cadmium chloride in vitro at the G2 stage decreased on days 14 and 30 of treatment with the complex.
The data on spontaneous chromosome aberration rates in cultures of human peripheral blood lymphocytes obtained in the past 30 years have been collected to form a database. The database contains the results of analysis of more than 330,000 metaphases in lymphocytes from more than 1200 subjects. The frequency of aberrant metaphases in the control group has been estimated at 0.0213 +/- 0.00085. No differences between sexes have been found with respect to either the total chromosome aberration rate or the rates of individual aberration types. The total chromosome aberration rate did not depend on age; however, it has been found that the number of fragments increased and the number of exchanges decreased with age. Smoking has been found to increase the frequency of chromosome aberrations in individuals with occupational hazards, but not in those who are not occupationally exposed to radiation or chemicals. Alcohol consumption increased the frequency of paired fragments, whereas the frequencies of other aberrations did not differ from the control values.
Spontaneous chromosome aberration rate in human blood lymphocytes was studied using the data collected during 30 years. Seasonal variation was found. An absolute maximum of chromosome aberration rate was observed in winter and a local maximum, in summer. In spring and autumn, this value decreased. There was a statistically significant trend towards higher frequencies of aberrant metaphases during the period studied. A periodic pattern of changes in the chromosome aberration frequency was found. The data fitted a sinusoid with a period of 4.5 years.
A cytogenetic examination carried out in the inhabitants of Seversk (Tomsk oblast) and workers of the Siberian chemical industrial complex (a complex of nuclear-chemical and fuel plants), living in the same town, revealed unusually high level of spontaneous chromosomal variability both in control and industrial groups (total irradiation doses 1.8 to 3.7 and 9.3 to 15.7 Gy, respectively). The frequencies of cells with chromosomal aberrations (estimated per 100 cells) in control and industrial groups were 4.69, 6.04, and 6.64, respectively, and the total number of aberrations constituted 6.93, 8.47 and 12.06, respectively. These frequencies were several times higher compared to the summarized literature data on the control levels. The high average aberration level was caused by the elevated proportion of chromatid-type aberrations and paired fragments. The reasons for this are unclear. The levels of radioactive background and chemical air pollution in the town were not increased.
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The results of population cytogenetic studies performed by a standard technique in one laboratory during 1987-1992 are summarized. Variations in the rate of spontaneous chromosomal aberrations were found in lymphocyte culture derived from individuals employed in the nonindustrial sphere and in the administrative sector of the chemical industry. The proportion of cells with chromosomal aberrations is 1.56 +/- 0.10% in the first group and 2.78 +/- 0.15% in the second one. The ratio of types of aberration is similar in both groups. No differences were observed in the rate of spontaneous chromosomal aberrations as related to the extent of chemical pollution of place of residence.
Cytogenetic analysis of lymphocytes was performed in 36 preparatory workers engaged into rubber shoes and general mechanical rubber goods production. Preparatory workers and management staff had the same chromosomal aberrations frequency. Although chromosomal aberrations frequency in employees of the enterprise appeared to be twice as much as that for general population, which proves hazardous factors of rubber production to afflict genofond of employees.
The article contains data on a cytogenetic monitoring of workers engaged in asbestos production, depending on duration of professional service and degrees of dust contamination of the air. The results of the cytogenetic analysis of the peripheral blood lymphocytes in 31 workers revealed the average rate of aberrant cells 1.78% in workers with professional service below 1.5 years, 2.43%--with more than 10 years of service, 2.72%--in the control group (the personnel not engaged in the production). The differences were statistically negligible.
In order to reveal possible genetic effects of the Chernobyl accident for human populations, a cytogenetic survey of 33 agricultural workers from 2 areas of the Kaluga Region with different radiation backgrounds (villages of Mladensk and Ogor) was conducted in 1989. At the time of investigation a dose of 137Ce for Mladensk was 3.7 ci/km2, that for Ogor--1.17 ci/km2. Lymphocyte cultivation was performed after the standard semimicromethod for 50 hours; about 155-300 cells were analyzed for chromosome aberrations of each individual, the total number of metaphase plates in 2 groups being 9360. One-factor dispersion analysis has shown that the rate of exchanges of a chromosome type, specific for radiation, was higher in the workers of the village of Mladensk than in the workers of Ogor (p less than 0.05). Thus statistically significant differences in the rate of metabolic aberrations of a chromosome type were revealed in the two study groups with different radiation backgrounds. A high sensitivity of cytogenetic analysis for population biological indication of irradiation was shown.
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The comparative in vivo and in vitro study of chromosomal aberrations and SCE induced by cyclophosphamide (CP) in macaca rhesus lymphocytes was performed. The dose of mutagenic exposure for quantitative estimation of effects was determined as a product of concentration of alkylating CP metabolites on the exposure time. The mutagenic effect caused by the same doses of CP (CP metabolites) appeared similar in vivo and in vitro. This suggests that the results obtained in adequate in vitro mutagen-testing experiments may be quantitatively extrapolated for the in vivo conditions.
A significant decrease in the baseline of sister-chromatid exchanges (SCEs) was observed in cultured human lymphocytes, if 5-bromodeoxyuridine (BrdU) was added after 60 h of culture, and the cells were harvested at least 24-30 h after BrdU exposure. This decrease is supposed to occur if at least one cell division takes place before the addition of BrdU. For cytogenetic monitoring of mutagenic environmental factors, using human lymphocyte cultures, it is assumed that two time periods are sufficient for comparison.
The number of sister chromatid exchanges (SCE) in a culture of human lymphocytes and the established cultures of Chinese hamster cells has been studied after the exposure to thiophosphamide and dipin at different stages of the cell cycle. The most pronounced effect is observed under the action of the mutagens at the G1 of the first cycle, prior to harvest. The SCE level becomes lower with the increase of the interval between the exposure to the mutagen and the time of 5-BUdR introduction. The number of SCEs per cell drops to the control level when the duration of the first interval is equal to that of the cell cycle. The results obtained prove the mutagen-induced impairments causing SCE formation to be repaired practically 100%, provided that at least one cycle of DNA replication took place.
Blood of practically healthy donors of both sexes (27 females and 23 males) was cultured under the standard conditions during 96 hours. Bromodeoxyuridine (BUdR) was added at the final concentration of 10 mkg/ml 28 hours before harvesting. The slides were stained with acridine orange and Giemsa for differential staining of chromatids. In each culture sister chromatid exchanges (SCE) were analysed in 50 cells, and the part of cells undergoing the first, second and third mitoses at the time of harvesting, was calculated. According to the mean number of SCE per cell, the distribution of individuals was consistent with the normal law, the mean being 6.525 and standard deviation--0.956. A significant heterogeneity in the speed of cell cycle of cultures was observed. The coefficient of variation for the part of cells undergoing the first mitosis was 50%, for the cells in the second mitosis--15%, and for the cells in the third mitosis--154%. Correlation analysis showed a positive dependence of the mean level of SCF upon the age of a donor and upon the part of cells in the second mitosis in this individual. No reliable correlation of the SCE level with the donor's sex was observed. The distribution of cells, obtained from the culture of one individual, was best approximated by beta-distribution, and the distribution of cells obtained from the cultures of different individuals--by gamma-distribution. In both there was obtained a satisfactory approximation by Pearson's distribution of the 1 type, and significant deviations were found from the normal, Poison's and the negative binomial distribution. The conditions were found of similarity of empirical distribution of SCE in cells to the normal one. For that, it is not the value of SCE for a separate cell that should be used as a unit of measurement, but the mean from the values of frequencies for 5-10 cells. Hence, it was shown that for the evaluation of the mean frequency of SCE with the precision of 1 exchange in separate individuals it is necessary to analyse 40 cells, and to observe the 15% increase of spontaneous SCE level under the action of deleterious factors--8 individuals are enough to analyse.
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A modified method of obtaining differential staining of sister chromatids is described. It is simple, rapid, and effective, and at the same time inexpensive and accessible, since it allows one to use available reagents. When 5-bromdeoxyuridine was administered 24 hours before fixation into the Chinese hamster cell culture the percentage of metaphases with a differential chromatid staining constituted 95--98, and when this substance was administered 28 hours before fixation into the human lymphocyte culture this percentage varied from 75 to 92, depending on the individual. The mean number of sister chromatid exchanges in human lymphocytes failed to depend on the time of fixation.
The cytogenetic examination of the population of the villages of Karakent and Ishan consisted of two directions: the study on the frequency of chromosome aberrations in the culture of lymphocytes and the diagnostics of anomalies and variants of karyotype. The frequency of chromosome aberrations of 40 individuals was studied. It is shown that the frequency of cells with chromosome aberrations of the individuals in different villages does not differ and on the average is 1,4%. The distribution of lymphocyte culture according to the number of aberrations corresponds to that of theoretical Puassonian. Chromatide breaks are the main type of the aberrations. Among 250 karyotypically examined individuals no evident structure reformations were found. In the caryotype of a 7-year old girl trisomia of the 21st autosome was detected. On the basis of differential staining of chromosomes by Hiemse's dye 18 individuals (7,2%) were diagnosed to have insignificant changes in morphology of some chromosomes, considered as variants of caryotype. In the majority of cases these changes were of a family nature. On the medical examination mnay individuals were diagnosed to have different pathological features, though we did not succeed in revealing any correlation between a certain microanomaly of chromosomes and a pathological feature.