Effects of vitamin supply on spontaneous and chemically induced mutagenesis in human cells.

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.

Effect of mitomycin C on distribution of chromatid exchanges and their dose dependency in resting human lymphocytes.

Cells distribution by the number of chromatid exchanges induced by mitomycin C corresponds to geometric distribution. The dependences of the number of chromatid exchanges and the number of fragments on the dose of the mutagen are described by exponential and linear curves, respectively. Quantitative regularities of mitomycin C-induced chromosome aberrations correspond to those of "monocentric" mutagens.

[Chromosomal abnormalities in lymphocytes from a patient with Werner's syndrome in intact culture and after treatment with halogenated analogs of thymidine]. / Khromosomnye anomalii u bol'nogo sindromom Vernera v intaktnoi kul'ture limfotsitov i posle vozdeistviia galogenovykh analogov timidina.

Four balanced chromosomal translocation, deletion of chromosome 15, and a break in chromosome 11 were detected in 100 G-banded metaphases of cultured lymphocytes of a patient with Werner's syndrome. We observed aneuploidy that included both trisomies and monosomies for various chromosomes. Halogenated analogs of thymidine in low doses increased significantly the incidence of chromosome aberrations accompanied by fragments. 5-Iododeoxyuridine induced lesions in centromeric regions of B-group chromosomes in 44.4% of all the cases of breaks. A hypothesis is proposed about the existence of a special mechanism for genetic control in changes in the cell nucleus and mitotic chromosome transformation. This mechanism can be manifested after the application of halogenated analogs of thymidine. The mutation involved in Werner's syndrome is presumably related to this mode of genetic control.

[Periodic variations of spontaneous chromosome aberration rate in human blood lymphocytes ]. / Vremennye kolebaniia spontannogo urovnia khromosomnykh aberratsii v kul'ture limfotsitov perifericheskoi krovi cheloveka.

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.

[The database for analysis of quantitative characteristics of chromosome aberration frequencies in the culture of human peripheral blood lymphocytes]. / Baza dannykh dlia analiza kolichestvennykh kharakteristik chastoty khromosomnykh aberratsii v kul'ture limfotsitov perifericheskoi krovi cheloveka.

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.

[Variabilities in chromosomal aberrations in human somatic cells]. / Zakonomernosti khromosomnoi izmenchivosti somaticheskikh kletok cheloveka.

Variabilities in the frequency of spontaneous chromosomal aberrations depend on subjective and objective factors, the stochastic nature of occurrence and recording of the aberrations. Due to the low frequency of spontaneous chromosomal aberrations, it is impossible to exactly assess their frequency on an individual basis. The low accuracy of estimating the individual frequency of spontaneous chromosomal aberrations while analyzing 100-1000 cells virtually allows the use of the individual average frequencies of chromosomal aberrations without taking into account the size of a sample to have an average group estimation of the frequency of chromosomal aberrations. The average frequencies of spontaneous chromosomal aberrations can be obtained to a rather high accuracy for individual groups when a sample comprises 50 to several hundreds of individuals. It is shown that the frequency of spontaneous chromosomal aberrations does not depend on sex and age. There is a significant variability in their frequency in relation to a season and to the year of a follow-up. Regular changes are found in the frequency of spontaneous chromosomal aberrations depending on the number of a month and on the year of a follow-up.

[New approach to evaluating mutagenicity by cytogenetic techniques]. / Novyi podkhod k otsenke mutagennosti tsitogeneticheskimi metodami.

A two-population model that satisfactorily describes the emergence of multiaberrant cells during spontaneous mutagenesis is proposed. The model is based on the conception of existence of two cell populations. In the first basic part, the cells are distributed by the Poisson law. In the second rather small part, those are distributed in a geometric fashion. It is suggested that such distributions result from mutations in reparation and replication genes. These mutations determine higher incidence of chromosomal aberrations distributed by the geometrical law.

Quantitative estimation of chromosome aberration frequency in cancer patients induced by endogenous and exogenous factors.

In patients with skin melanoma and colon cancer, cell distribution by the number of chromosome aberrations cannot be described by Poisson distribution, but corresponds to a bipopulation model combining the Poisson and geometric distributions. In contrast to the control, in patients with malignant tumors, cells with geometric distribution possess the majority of chromosomal aberrations.

[Unusually high level of chromosome variability in cultured human peripheral blood lymphocytes]. / Neobychaino vysokii uroven' khromosomnoi izmenchivosti v kul'ture limfotsitov perifericheskoi krovi cheloveka.

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.

[Karyotypic anomalies and chromosomal sites of increased fragility in colorectal cancer]. / Anomalii kariotipa i saity povyshennoi lomskiti khromosom pri kolorektal'nykh rakakh.

Karyotypic structural aberrations in tumor cells and chromosome constitutive fragile sites (cFSs) in peripheral blood lymphocytes were studied in ten patients with colorectal adenocarcinoma Most chromosome breakpoints (38 out of 40, i.e., 95.0%) were shown to be located within cFSs in tumor cells. Expression of 24 out of 137 cFSs in patients was higher than that in healthy donors. Four of these cFSs (6q26, 7q36, 16q23, and 17q21), were involved in the formation of nonrandom tumor cell chromosome markers most characteristic of colorectal neoplasms. The frequency of damages induced within these sites was analyzed in each patient. Expression of 7q36, 16q23, and 17q21 was increased in blood cells of patients carrying specific chromosome rearrangements with the breakpoints within these sites. The association between nonrandom chromosome aberrations in tumor cells and cFSs in normal cells is discussed.

[Effect of mutations on the dynamics of numbers of individuals with different genotypes in an isolated heterogeneous population]. / Vliianie mutatsii na dinamiku chislennostei osobei s razlichnymi genotipami v neodnorodnoi izolirovannoi populiatsii.

The overall (throughout the range) dynamics of the number of diploid individuals possessing n possible gene alleles in a given autosomal locus is studied in an isolated heterogeneous population. The significant influence of new mutations on overall dynamics is shown. It is demonstrated that, under certain conditions, the selection mechanism might have a greater effect on the dynamics of number of individuals with different genotypes in the isolated heterogeneous population than on mutation and "death-reproduction" mechanisms.

[Selection dynamics in a heterogeneous population]. / Dinamika otbora v neodnorodnyi populiatsii.

The dynamics of the number of diploid individuals with possible n > or = 2 alleles of a gene located not in a sex chromosome was studied in heterogeneous isolated population. It was demonstrated that if only selection is accounted for, the number of individuals carrying alleles that do not provide maximal selective advantage approaches zero as the time of observation increases, whereas the number of individuals with various genotypes, but with a maximal selective advantage, approaches non-zero stationary values depending on their initial numbers. It was established that under certain conditions and even if processes of death-multiplication are taken into account, the mechanism of selection may have a dominating effect on population dynamics.

[Expression of lysosomal enzymes in pregnancy]. / Issledovanie ékspressii lizosomnykh fermentov pri beremennosti.

Activities of 6 lysosomal enzymes in leukocytes and 3 enzymes in blood serum were studied in pregnant women. Only activity of beta-D-glucosidase was not altered within all the pregnancy of I-III trimesters, while activity of all the other enzymes studied was distinctly increased to the third trimester. Use of the data obtained in prenatal diagnosis of lysosomal storage diseases is discussed.

[Use of an information-search diagnostic system for recognizing acute hereditary metabolic diseases with early lethal outcomes]. / Ispol'zovanie informatsionno-poiskovoi diagnosticheskoi sistemy dlia raspoznavaniia ostrotekushchikh nasledstvennykh boleznei obmena s rannim letal'nym iskhodom.

An information retrieval diagnostic system for hereditary metabolic diseases that are characterized by acute progression and early fatal outcome was developed. The system includes four databases: a list of nosological forms (n = 152), a list of clinical symptoms and characteristics (n = 1094), clinical portraits of every disease, and a list of biochemical characteristics (n = 1072). The system describes each disease as follows: clinical phenotype, etiology, genetics, pathogenesis, biochemical phenotype, paraclinical investigations, differential diagnosis, treatment, and prevention.

[Spread of mutations in an inhomogeneous environment with respect to migration. III. A closed model of population dynamics with a arbitrary type of mutation and analysis of the effect of selection mechanisms and "death-reproduction"]. / Rasprostranenie mutanta v neodnorodnoi srede obitaniia s uchetom migratsii. III. Zamknutaia model' dinamiki populiatsii pri proizvol'nom tipe mutanta i analiz vliianiia mekhanizmov otbora i "gibeli-razmnozheniia".

A closed mathematical model of population dynamics for an arbitrary mutant type was developed based on results obtained previously. The model considers the number of individuals with different genotypes, their random and constrained movements across the range, mechanisms of selection and Death-reproduction, and different conditions of the process at range boundaries. The influence of mechanisms of selection and Death-reproduction on integral parameters of the studied process was analyzed.

[An analysis of the chromosomal combinations in dicentrics with induced telomeric fusion]. / Analiz sochetanii khromosom v ditsentrikakh pri indutsirovannom telomernom sliianii.

Chinese hamster heteroploid cell culture was treated by colcemide for 42 h, of which within the first 17 h by 5-bromedeoxyuridine. Dicentric chromosomes, that were formed at the 2nd mitosis after colcemide administration, were analysed using G-banding. Of 211, only 40 were made of heterological dicentrics. Other 171 dicentrics were formed by telomeric fusion of autological chromosomes. No correlation was found between the length, centromeric index and frequency of dicentric formation. A probability of telomeric fusion of chromosomes determined by nucleotide sequences specific for each chromosome is proposed.

[Mathematical modeling of the dynamics of frequency of the mutation process. I. Age features of SA frequency dynamics tendency]. / Matematicheskoe modelirovanie dinamiki chastot mutatsionnogo protsessa. Soobshchenie I. Vozrastnye osobennosti tendentsii dinamiki chastot SA.

A mathematical method for modelling SA frequency dynamics tendencies, depending on age, for different fixation moments and in general for the whole interval of observation is suggested. The criteria of remainder dispersion attitude is used for choosing an optimal model. The initial hypothesis about discrepancies distribution law is used for checking adequateness of the optimal model to the research process. In addition, aposteriory trust intervals are built for the initial and forecast SA frequency values and the hit into them corresponding the experimental values of SA frequencies is controlled. An example of practical realization of the model proposed is considered and the results obtained analysed.