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Biomedical subjects

L A Vasil'eva

Publications and source records attributed to L A Vasil'eva.

At least 19 recordsLinked to original sources

Expression of mRNA for several enzymes of xenobiotic detoxification in normal and spontaneously transformed mesothelial cells and mesothelioma cells of rats.

Expression of mRNA for the mdr1 gene, cytochrome P450 isoforms 1A1 and 1B1, Ah receptor, and ARNT protein regulating the concentration of cytochrome P450 mRNA was compared in normal and spontaneously transformed mesothelial cells and mesothelioma cells from rats. Expression of cytochrome P450 1A1 and 1B1 mRNA decreased in transformed mesothelial and mesothelioma cells compared to normal mesothelial cells. mRNA for the mdr1 gene was undetected in normal mesothelial cells. Expression of mRNA for the Ah receptor and ARNT protein did not differ in cultured cells.

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[Analysis of the expression system of gene radius incompletes in Drosophila melanogaster].

The genetic expression system of gene radius incompletes was studied by substituting regions of chromosome 3 from line th st sr ca, which has drastically reduced ri expression, to regions of chromosome 3 from a "selection" line ri s having very high expression of this gene. Virtually all chromosome 3 was shown to carry polygenes controlling phenotypic expression of oligogenic mutation ri. Chromosome regions making large (as well as small and even negative) contributions to sizes of the distal and proximal fragments of the latitudinal wing vein were found. These results suggest that the genetic system of expression does not correspond to the generally accepted postulates of K. Mather on equal, small, and additive contributions of polygenes.

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[The effect of isogenization on the phenotypic manifestation of quantitative traits in Drosophila melanogaster].

A comparative analysis of the phenotypic values of the proximal and distal fragments of the radial wing vein was carried out in heterogeneous lines of Drosophila melanogaster and in isogenic lines derived from them with the help of a balancer line. The mean values of the traits in the isogenic lines were shown to significantly differ from the corresponding values in the "parental" heterogeneous lines. Apparently, the change in the trait values was caused by a double recombination exchange between the inverted and the "normal" chromosomes, which suggests partial crossing over suppression in the balancer lines.

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[The role of macrophages in asbestos-induced carcinogenesis].

Data available on the pathways of asbestos (fibrous) carcinogenesis still leaves much to be desired. Asbestos is regarded as a non-genotoxic substance by most researchers. There is insufficient evidence on the interaction of fibres, target-cells and macrophages. Macrophages secreted proteins (ca. 450 kD) to inhibit proliferation of intact mesothelium and cytoxine (3-5 kD) which stimulated the cellular sensitivity of intact mesothelium and mesotheliomas to the toxic influence of asbestos. It was suggested that the effect was due to the triggering of intrinsic causation of cell death. Like any other fibres, carcinogenic effect of asbestos could be accounted for by such significant factor as active oxygen radicals. When exposed to asbestos, both intact mesothelial and mesothelioma cells and macrophages synthesized those substances. Free radical-like substances in conjunction with macrophage-conditioned media produced toxic effect on mesothelial cells. The role of active oxygen radicals in fibre-induced carcinogenesis is discussed.

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[Comparative analysis of MGE 412 patterns in 18 isogenic lines of Drosophila melanogaster].

Comparative analysis of patterns of mobile genetic element 412 was conducted in 18 isogenic lines of Drosophila melanogaster isolated in three isogenic experiments in 1987 through 1999. Twelve "extra-hot" isogenization sites (in 15-18 lines) and 23 "hot" isogenization sites (> or = 10 lines) were found; of these, 19 occurred in the original heterogeneous line. These sites virtually do not overlap with hot induction sites of transposition. Sites of the latter group generally retain their positions during isogenization. It was shown that no more than 20% of the new sites were brought from the balancer by double recombination, while inbreeding and outbreeding caused 80% of them. Different factors were shown to have different hot isogenization sites. A similarity tree was constructed for the patterns of 18 isogenic lines. The maximum peak of the tree was very low (< 0.25), i.e., the isogenic lines are more similar to than different from one another. The tree was subdivided into subtrees. The division was in good agreement with the isogenization groups corresponding to individual isogenization experiments. Significant correlation was found between the total fragment length and the number of new sites per lines.

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[Induction of MGE 412 transposition in an isogenic strain of Drosophila melanogaster by different doses of ethanol fumes].

The effect of treatment of males from an isogenic Drosophila melanogaster strain by limiting doses of ethanol fumes on transpositions of MGE 412 was examined. Validity of the phenomenon of transposition induction was demonstrated. We estimated rates of induced transposition (approximately 10(-2) events per site, per sperm, per generation versus < 10(-3) in control) and showed dose dependence of the rate on the exposure time of the males to ethanol fumes. Experiments with alcohol treatment at limiting doses must end either in death of the individuals or bursts of genetic variability in their progeny. In terms of genetics of an individual, this may mean loss of vital hereditary basis followed by mass degradation of the progeny of the "hard drinkers." In terms of populations genetics, this mode of MGE transposition induction can rapidly create a burst of novel genetic variation, which, apart of great losses, may generate a number of advantageous individuals, i.e., be significant for population survival in new, stressful environments.

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Cytotoxic effects of macrophages and asbestos on transformed rat mesothelial cells.

Asbestos produced a cytotoxic effect on transformed cells of rat pleural mesothelium and on IAR2 epithelial cells and Rat1 fibroblasts transformed by ras oncogene, but not on normal cells of these strains under conditions of coculturing with peritoneal macrophages. Contact of mesothelioma cells, but not macrophages with asbestos was necessary and sufficient for attaining the cytotoxic effect. Macrophage-conditioned medium potentiated asbestos cytotoxicity for transformed mesothelial cells, but not for IARS-ras and Rat1-ras.

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[Induction of MGE 412 transposition individually by heat and cold shock in spermatogenesis in Drosophila males].

Effects of temperature treatment (heavy heat shock, HHS; heat shock, HS; and cold shock, CS) on the daily productivity of treated males in different spermatogenesis stages have been studied in isogenic line 51 of Drosophila melanogaster. The average productivity was shown to substantially decrease in all cases. The sum of the HS and CS contributions to this decrease was nearly equal to the HHS (the combined HS and CS) contribution, i.e., these contributions were almost additive. The temperature treatments did not kill mature sperm. In the control, mating productivity of day 1 exceeded that of the next day at least by 10-20%. Each day, most sperm in matings was new, i.e., matured during that day. Transposition induction of MGE 412 was studied at four spermatogenesis stages after HS and CS. Both temperature treatments were effective but CS had a more pronounced inducing effect. Most temperature-induced transpositions occurred at stage 3 (meiosis) and 4 (spermiogenesis). The day rates of transpositions at different stages were estimated. After HS at the meiosis stage, lambda = 0.11 events per initial MGE copy per sperm per day of mating, which is approximately equal to the previous estimates after HHS. After CS at the meiosis stage, lambda = 0.51. The transposition hot sites (including the previously known 43B and 97DE as well as a number of new sites) were detected. The lists of transpositions after CS completely included the corresponding lists after HS, which suggests similarity of induction mechanisms underlying CS and HS.

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[On carcinogenic effects of sulfate copper and nickel ore].

Underground mines are places for extraction of three types of copper and nickel sulfide ores: rich, copper and incorporated--those three ones differ in mimeralogic and chemical contents. Experimental evaluation of carcinogenic effects obtained during intratracheal administration of copper and incorporated ores indicates the certain carcinogenic activity of the dust with 0.49-1.14% nickel and 1.9-5.8% copper content--therefore a unified MAC for all the stated dust types could be suggested.

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Cytokine secreted by rat macrophages and inhibiting proliferation of mesothelial cells.

Rat peritoneal macrophages and human peripheral blood monocytes secrete a protein with a molecular weight of 450 kDa, which specifically inhibits proliferation of cultured rat pleural mesothelial cells, but not fibroblasts and epitheliocytes. Protein secretion does not depend on the activation of macrophages. This cytokine is not a cobalamin-binding protein and has no arginase activity.

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[Prolongation of MGE 412 transposition induction after gamma-irradiation in an isogenic line of Drosophila melanogaster]].

The dose dependence of the rate of gamma-induced transpositions and consequent dynamics of the MGE 412 pattern after gamma-irradiation were investigated in isogenic line 49 in generations F1, F12, F140, and F170. It was shown that the results on dose dependence of transpositions was very similar with the corresponding results of the classic works by Timofeeff-Ressovsky et al. (1935). It is suggested that the transcribed copies of retrotransposon 412 "cure" gamma-radiation-induced double-strand DNA breaks. The phenomenon of prolongation of MGE transposition induction during early generations after treatment was shown. In this period (F1-F12), the maximum transposition rate (lambda approximately equal to 2 x 10(-2) events per MGE copy, per haploid genome, per generation) and the maximum number of heterozygous MGE copies were achieved. In the late generations (F140 and F170), the reduced induction level (lambda approximately 10(-3) was established. In the population of effective size Ne = 2000 individuals, this corresponds to the state when lambda >> 1/4Ne, i.e., when the transposition flow prevails over the MGE copy loss by genetic drift. These data together with some indirect evidence argue for the hypothesis that the spontaneous transposition rate is proportional to the average number of heterozygous MGE copies per diploid genome.

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[Effect of genotypic environment on phenotypic manifestation of radius incompletus mutation in Drosophila melanogaster].

Genetic analysis of marked regions of Drosophila chromosome 3 was performed in order to localize the "effective factors" of the polygene system that controls the expression of the limiting mutation in radius incompletus, the major-effect gene. The marked homozygous strain with genotype th st ri sr ca was crossed with the "selection" riSN strain. Contributions of the marked regions of chromosome 3 to the expression of the proximal and distal fragments of the wing radial vein were estimated. It was demonstrated that the th-st region of the marked strain contained a polygene determining a large positive contribution to the lengths of both fragments, whereas the st-ri region contained a polygene determining a large negative contribution to the length of the distal fragment compared to the riSN strain. Crossings were performed between strains that contained Mendelian mutations of the ri, ve, and vn major-effect genes of the wing vein patterns. Unexpectedly, a strong, non-additive effect of the interaction between these mutations was found. This effect was expressed as a complete disarrangement of the wing vein pattern. Each participant gene may be regarded as a large-effect polygene relative to the other genes.

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[Heavy heat shock induces genetic variation in a polygenic system of a quantitative trait in Drosophila].

Results of two experiments dealing with positive and negative selection on the quantitative trait radius incompletus in an isogenic line of Drosophila melanogaster after heavy heat shock (HHS) are presented. Selection was not effective in the control without HHS. In experiment 1, in which offspring of HHS-exposed males lacked transposition induction, selection also was ineffective. By contrast, selection was highly effective in offspring of males that responded to HHS exposure by transposition induction. Thus, HHS, which is not mutagenic, generates genetic variation in a polygenic system of a quantitative trait via transpositions and excisions of mobile genetic elements. In experiment 2, positive and negative selection was conducted in three replicates, which showed concerted dynamics of the selected trait. This means that the trait dynamics is mainly related to the nearly deterministic process of accumulation of active polygenic alleles rather than to genetic drift. The induced variation of polygenic systems promotes rapid selection of "champion" genotypes. This variation is probably associated with "soft" modification of polygene expression by adjacent MGE copies.

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[Response of the MGE 412 pattern to truncation selection of a quantitative trait in an isogenic line of drosophila after severe heat shock (SHS)].

Positive and negative selection on the total length of two fragments of an interrupted longitudinal wing vein in an isogenic line of Drosophila melanogaster was accompanied by changes in the genomic localization pattern of MGE 412. Strong truncation selection was conducted in the population of effective size Ne = 160 for 50 generations. Twenty-six out of 35 polymorphic HHS-induced segments of MGE localization behaved as independent copies and markers, whereas 9 segments proved to be selective. The second group included "hot" segments of HHS transposition induction (43B, 97E, etc.). Thus, final consensus patterns of induced MGE transpositions have a random and an adaptive component in generation 50 of positive and negative selection. Selective patterns probably include modifier MGEs, which generate induced genetic regulatory variation of polygenes controlling the selected quantitative trait in the isogenic line after HHS.

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[Methodological approaches to the study of the carcinogenic properties of substances].

Since the methods of investigation of carcinogenicity of different agents have changed drastically, relevant manuals need to be revised and supplemented. A new concept of carcinogenic agents evaluation, criteria for their selection and study are discussed. Working out of criteria for establishing priorities of hazardous substance selection is of vital importance.

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[Comparative contribution of different genetic factors in induction of MGE transpositions under isogenization].

Localization patterns of mobile genetic element 412 in polytene chromosomes of larvae from the control (riC) line, the balancer line, the F1 and F2 generations of the isogenization scheme, and 10 final isogenic lines were obtained and compared. The contributions of the recombination transfer of mobile genetic element copies from the balancer line, the outbreeding of control and balancer lines, and the inbreeding of isogenized lines to the rate of transposition were determined and estimated. These constituted < 0.187, < 0.30, and > 0.207 events per initial mobile genetic element copy per isogenized haploid genome per isogenization, respectively. During consecutive steps of isogenization (F1-F2-isogenic lines), the total transposition rate decreased: 2.09, 1.78, and 0.69. This was explained in terms of the existence of large selective and random losses in the variability of mobile genetic elements within the sites of their patterns during isogenization. The existence of a recombination transfer does not change the main conclusions and estimates regarding isogenization-induced transpositions.

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[Population dynamics of the response of the genomic pattern of the mobile genetic element Dm412 in Drosophila on selection for a quantitative trait].

In an isogenic line of Drosophila melanogaster carrying the Mendelian mutation radius incompletus, selection for the total length of two segments of the disrupted longitudinal wing vein was conducted. After gamma-irradiation at a dose of 13 Gy, positive and negative truncation selection became highly effective and was completed in 50 generations. The pattern of mobile genetic element Dm412 was almost completely fixed in the course of selection. In the positive direction of selection, fixations of mobile genetic element (MGE) sites exceeded losses; in the negative direction, this relationship was reversed. The number of MGE sites in the pattern increased from 23 to 33 and to 26 in the positive and negative directions, respectively. The mean heterozygosity of MGE sites decreased respectively ten and six times. The dynamics of some sites (6F, 43B, 66A, 69E, and others) corresponded to that expected with an adaptive response to selection. Two out of these sites (43B and 66A) were previously assigned to hot sites of Dm412 transposition induced by heat shock. Fixation and loss of sites continued on average for tens of generations. Four hypotheses describe the relationship between patterns of polygenes and MGE in the context of explanation of the above facts: (1) genetic drift; (2) the linkage of MGE and polygenes without modification of the latter (hitchhiking); (3) the linkage and modifying effect of MGE on polygenes linked with them; (4) the selection of the "champion" pattern of polygenes and a random or adaptive MGE pattern linked with it. Hypotheses 1 and 2 are unlikely, hypothesis 3 is possible in the case of other selection modes, whereas hypothesis 4 seems to be most plausible.

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