[Analysis of DNA and chromosome damage by the methods of molecular cytogenetics].

The main hybrid techniques of molecular cytogenetics are described. Methodological aspects of combination of fluorescence in situ hybridization (FISH) with the comet assay and micronuclei (MN) test are discussed along with results of their application to evaluate and locate DNA and chromosome damage in the genome. The experience of the authors with the application of FISH in combination with the comet assay and MN test are reported.

[Investigation of chromosomal anomalies by fluorescence in-situ hybridization (fish) in Armenia].

Prenatal and postnatal molecular-cytogenetic investigations of 75 patients have been performed. 3-stage international standard of patients' examination was used, including general clinical examination, investigation by the methods of conventional cytogenetics and molecular-cytogenetic fluorescence in-situ hybridization (FISH) analysis. On the basis of cytogenetic investigation we can conclude that in 25% of cases of complex chromosomal anomalies the cytogenetic diagnosis, obtained by means of conventional karyotyping, needed further specification. Only in 50% of these cases FISH-investigations confirm the results, received on the basis of conventional cytogenetics. In other cases diagnosis was specified or changed. The investigations were carried out with consultations of Institute of Medical Genetics (University of Zurich). Some cases of chromosomal pathology, representing scientific interest, were included in the European Cytogeneticists Association Register of Unbalanced Chromosomal Aberrations (ECARUCA).

[DNA comet assay for evaluation of genotoxic effects in risk groups]. / Primenenue metoda DNK-komet dlia otsenki genotoksicheskikh éffektov v gruppakh riska.

DNA comet assay (CA), gel electrophoresis of single cells, is effective in evaluating the genetic (genotoxic) effects of endogenous and exogenous agents. CA was used to study the extent of spontaneous or UV-induced DNA damages in the leukocytes in two groups at genetic risk: in Chernobyl accident liquidators and patients with familial Mediterranean fever (FMF). There was a significant increase in the number of UV-induced and excision repair-mediated DNA breaks in both risk groups as compared to control samples. The spontaneous extent of DNA breaks in the cells of the liquidators and FMF patients were similar to those in the controls. The extent of oxidative DNA damages detected during incubation with the endonuclease enzymes formamidopyrimidine glycosylase and endonuclease III were also determined in FMF patients. There were no statistically significant differences in the extent of oxidative DNA damage in the cells of FMF patients as compared to the controls. The findings give grounds to recommend CA for biomonitoring of genotoxic effects.

[An evaluation of the mutagenic activity of the air pollutants in the area of a plant for the manufacture of synthetic rubber by using Tradescantia (clone 02) as the test object]. / Otsenka mutagennoi aktivnosti zagriaznitelei atmosfernogo vozdukha v raione zavoda po proizvodstvu sinteticheskogo kauchuka s primeneniem test-ob''ekta tradeskantsii (klon 02).

The mutagenic effects of atmospheric pollutants of synthetic rubber works on the frequency of point mutations in somatic cells of stamen hairs (CSH) of Tradescantia (clone 02) was studied under the condition of functioning or nonoperating shops. It was shown that temporary stopping of shops led to a decrease in the number of recessive mutations in CSN to the level 1.5 times higher than the control one. It increased during shop functioning to 0.21%. The cells moving off from the source of pollution led to a decrease in mutation frequency. The changes in the frequency of genetically indefinite mutations and morphological traits were also registered.

[Intergroup differences in anticlastogenesis]. / Mezhgruppovye razlichiia antiklastogeneza.

The paper deals with the mechanisms of anticlastogenesis protection of chromosomes in cultured human cells, which depend on many external and internal factors and may vary in genetic risk groups and in individuals. It also analyzes the role of repair and metabolic disturbances in the observed inter- and intragroup differences in the efficiency of protective action in model test systems. Results of comparative analysis of the efficiency of various interferons in the cultured cells from patients with bronchial asthma are presented. The paper first provides evidence for attenuated protective effects in the cultured lymphocytes from patients with xeroderma pigmentosum or chronic recurrent urticaria as compared to those from healthy donors. Prospects of and optimal methodological approaches to the study of anticlastogenesis in human cells are discussed.

[Genetic load in a rural population in the Armenian SSR]. / Izuchenia geneticheskoi otiagoshchennosti sel'skoi populiatsii v Armianskoi SSR.

The reproductive function of women was analysed using interviews in zones with different levels of pesticides application. Increase in frequency of abnormal pregnancies in the zone of high level of pesticides application is shown. The main part of cases with hereditary pathology constituted the children with mental retardation. On the basis of surnames differentiation analysis, the relative homogeneity of structures of populations studied was demonstrated. The cytogenetic analysis only revealed small increase in SCE levels and no changes in the levels of aberrations of chromosomes in cultures of lymphocytes of rural workers contacting pesticides.

[The cytogenetic effect of natural mutagenesis modifiers in a human lymphocyte culture. The action of aminobenzamide during the gibberellic acid induction of chromosome aberrations]. / Tsitogeneticheskii éffekt estestvennykh modifikatorov mutageneza v kul'ture limfotsitov cheloveka. Deistvie aminobenzamida pri induktsii aberratsii khromosom gibberellovoi kislotoi.

The 3-aminobenzamide sensibilization of the cytogenetic activity of gibberellic acid in the culture of human lymphocytes has been investigated. Two-three-fold increase of the chromosome aberrations induced by gibberellic acid, irrespective of the time of 3-aminobenzamide addition to the cultures (the 28th, 46th, 72th hrs of the cultivation) is shown.

[The cytogenetic effect of natural modifiers of mutagenesis in a human lymphocyte culture: the modification of the mutagenic effect by recombinant interferon in vitro in the lymphocytes of bronchial asthma patients and of healthy donors]. / Tsitogeneticheskii éffekt estestvennykh modifikatorov mutageneza v kul'ture limfotsitov cheloveka: modifikatsiia mutagennogo éffekta rekombinantnym interferonom in vitro v limfotsitakh bol'nykh bronkhial'noi astmoi i zdorovykh donorov.

The significant protective effect of recombinant interferon in the cultures of lymphocytes of healthy donors and patients with bronchial asthma has been revealed. The cytogenetic damage were stimulated by alkylating agents thioTEPA and photrin during their administration at the stages Gi-S of the cell cycle. No differences were revealed in the action of mutagens and protector in the patients and healthy persons.

[Effect of interferon on the number of cytogenetic disorders occurring in human cultured lymphocytes treated with thio-TEPA and fotrin]. / Vliianie interferona na kolichestvo tsitogeneticheskikh narushenii, voznikaiushchikh v kul'tiviruemykh limfotsitakh cheloveka pri obabotke tioTEF i fotrinom.

The paper deals with the modifying effects of natural (leukocytic) and synthesized (recombinant) interferons on the number of cytogenetic injuries in the cultured lymphocytes of human peripheric blood after exposure to alkylating chemicals--thio-TEPA and fotrin. The analysis of chromosomal aberration levels is suggestive of a significant protective effect exerted by interferons. The addition of the recombinant interferon increased the number of sister chromatid exchanged frequency in mutagen treated variants. The application of the test system that involves two types of interferon made it possible to reveal differences in their cytogenetic effect during the protector-sensitive period of cultivation.

[Complex evaluation of the cytogenetic activity of plant growth regulators in different test systems]. / Kompleksnaia otsenka tsitogeneticheskoi aktivnosti nekotorykh reguliatorov rosta rastenii v razlichnykh test-sistemakh.

The cytogenetic activity of plant growth regulators is investigated in three different test systems. It is shown that three substances (hydrel, dihydrel, camposan) induce no chromosome breaks. MAH-I (maleic acid hydrazide monosodium salt) increases the mutagenic activity in all three investigated test-systems (in somatic and generative cells of rats and in the culture of human lymphocytes). The recrystallized MAH (II) and alar demonstrate an increase in the level of chromosome aberrations in the culture of human lymphocytes and in the bone marrow of rats.

[Mutagenic action of latex polymerization stabilizers in various test systems]. / Izuchenie mutagennogo deistviia stabilizatorov polimerizatsii lateksov v razlichnykh test-sistemakh.

The cytogenetic activity of latex polymerization stabilizers (monoethanolamine, triethanolamine and neozon-D) is investigated in three different test systems. It is shown that monoethanolamine and triethanolamine are weak inductors of chromosome breaks in the culture of human lymphocytes and in the Crepis capillaris seeds and induce low levels of gene mutations in the Ames systems. The third stabilizer--neozon-D manifests higher mutagenic activity and definite cytotoxic effect. Monoethanolamine and triethanolamine as to their weak mutagenic effect are recommended as preferable stabilizers to be used in the latex industry.

[Cytogenetic effect of natural mutagenesis modifiers in a human lymphocyte culture. The action of caffeine during the induction of chromosome aberrations by gibberellic acid]. / Tsitogeneticheskii éffekt estestvennykh modifikatorov mutageneza v kul'ture limfotsitov cheloveka. Deistvie kofeina pri induktsii aberratsii khromosom gibberellovoi kislotoi.

Caffeine sensibilization of the cytogenetic activity of gibberellic acid in the culture of human lymphocytes was investigated. A four-five-fold increase in the level of chromosome aberrations by addition of caffeine into the culture with gibberellic acid on the 29th, 46th and 72nd hour of cultivation was revealed. Application of sensitizers of the chemical mutagens' action is recommended to study weak mutagenic activity of chemicals in routine test systems.

[Modelling modification of chemical mutagenesis in human cells. III. Linear index of protection as the standardized criterion of modification]. / Modelirovanie modifikatsii khimicheskogo mutageneza v kletkakh cheloveka. Soobshchenie III. Lineinyi pokazatel' zashchity--unifitsirovannyi kriterii modifikatsii.

The effect of substances with radioprotective activity, APAETP 2,3 (aminopropylaminoethylthiophosphoric acid 2,3), APAETP 3,3 and cystaphos, on chromosome aberrations, induced by thioTEPA in the culture of human lymphocytes was investigated. It is shown that the obtained curves "concentration -- effect" for thioTEPA can be described by equations rho = 1 -- e-(KC + alpha)2 and X = E -(KC + alpha)2 --1 for aberrant cells and for chromosome breaks in the presence of the investigated substances. On the basis of comparison of angle coefficients of regression the unificated characteristic of the efficiency of chemical mutagenesis is proposed: the linear protection index (LPI), with generalizes the effect of modificators in chemical mutagenesis.

[Modelling of a modification of chemical mutagenesis in human cells. II. The dependence of the effect on the time of culture treatment]. / Modelirovanie modifikatsii khimicheskogo mutageneza v kletkakh cheloveka. Soobshchenie II. Zavisimost' éffekta ot vremeni obrabotki kul'tur.

The influence of 2,3-aminopropylaminoethylthiophosphoric acid (2,3-APAETP) on the effect of the alkylating agent, thio TEPA, is investigated at different times of cultivation of human peripheral lymphocyte culture. The analysis of correlation equations shows that the results are described by the polynomes of 4-degree in variants treated with thioTEPA and 2,3-APAETP. The protector effect of 2,3-APAETP is determined not by the time from the culture stimulation but the time between the moment of culture treatment with 2,3-APAETP and thioTEPA and the moment of the fixation. It is shown that the points of maximal sensitivity of the cell cycle to thioTEPA and to the protective effect of 2,3-APAETP are similar.

[Modeling modification of chemical mutagenesis in human cells. 1. Elimination of chromosomal aberrations]. / Modelirovanie modifikatsii khimicheskogo mutageneza v kletkakh cheloveka. Soobshchenie I. Eliminatsiia aberratsii khromosom.

Elimination of chromosome aberrations was studied in populations of dividing cells. For this purpose, on the basis of the corresponding theory of Carrano-Heddle assuming the Poisson distribution, a theory is advanced by the authors based on geometrical distribution, describing the distribution of lesions caused by the action of tioTEF. Parameters of elimination are obtained observed in case of addition of a protector, aminopropy-laminoethylthiophosphoric acid (APAETF) in a lymphocyte culture of human peripheral blood. It is shown that the addition of the protector diminishes the probability of the transmission of chromosome aberrations to daughter cells.

[Study of the cytogenetic activity of radioprotective agents in a human lymphocye culture. III]. / Izuchenie tsitogeneticheskoi aktivnosti radioprotektorov v kul'ture limfotsitov cheloveka. Soobshchenie III

Distribution of chromosome aberrations in cells of human lymphocyte cultures treated with mutagenic agent thioTEPA and protectors--aminopropylaminoethyl thiophosphoric acid (grammaphos) cystaphos and 5-metoxytriptamine (mexamine) was studied. It is shown that the empirical distribution of aberrations in cell is described by geometrical distribution.