Rats Selected for Different Nervous Excitability: Long-Term Emotional-Painful Stress Affects the Dynamics of DNA Damage in Cells of Several Brain Areas.

The maintenance of genome stability is critical for health, but during individual ontogenesis, different stressors affect DNA integrity, which can lead to functional and/or structural changes in the cells of target organs. In the nervous system, cell genome destabilization is associated with different neurological and psychiatric diseases, but experiments in vivo, where a link between stress and DNA instability has been demonstrated, are relatively rare. Here, we use rat strains selected for the contrast excitability of the tibialis nerve () and nonselected Wistar rats to investigate the reasons for individual differences in developing post-stress pathologies.

Pheromone of grouped female mice impairs genome stability in male mice through stress-mediated pathways.

Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the role of chemosignals in the regulation of mouse physiology and behavior in response to social crowding.

[Antimutagenic effect of chemosignals from isolated female house mouse on male germ cells (Mus musculus L)].

The influence of chemosignals from isolated mature females of the CBA line on level of spontaneous and radiation-induced meiotic disturbances in spermatocytes I of males of the same line was studied. Using an ana-telophase method, 24-hour exposure of males to soiled bedding containing isolated females chemosignals was shown to lead to a significantly lower frequency of chromosomal aberrations and other meiotic disturbances in spermatocytes I as compared to males kept on clean bedding. The same effect of female chemosignals was found in the reproductive cells of irradiated males (4 Gr).

[Chemosignals from isolated females have antimutagenic effect in dividing the cells of bone marrow from male mice of the CBA line].

A level of X-ray induced mitotic disturbances in the cells of the bone marrow of male mice was studied under the modifying influence ofchemosignals from isolated adult female mice of the CBA line. It has been shown that the frequency of chromosomal aberrations in irradiated (4 Gr) males after exposing them for 24 hours on bedding soiled with female chemosignals is lower than in irradiated males in cages with clean bedding. The mechanisms and importance of the antimutagenic effect of female house mouse chemosignals are discussed.

[Balance hypothesis of action of socially significant volatile chemosignals on reactivity of chromosome machinery of the bone marrow dividing cells in the house mouse Mus domesticus L].

Volatile chemosignals released by female CBA laboratory mice have been shown to produce action of different direction, depending on conditions of performance of experiment, on chromosome machinery of bone marrow cells in syngenic adult males. Thus, chemosignals secreted into environment by isolated adult females decrease frequency of mitotic disturbances in bone marrow dividing cells in male recipients as compared with spontaneous level in control animals. At the same time, 2,5-dimethylpyrazine - pheronome released only by high density caged females - increases frequency of mitotic disturbances.

[Action of two pyrazine-containing chemosignals on cells of bone marrow and testes in male house mouse Mus musculus L].

Evolutionary conservative chemosignal 2,5-dimethylpyrazin that is pheromone in female mice has been shown to increase frequency of mitotic aberrations analyzed with aid of metaphasic and ana-telophasic analysis in bone marrow cells. Replacement of one of methyl radicals in the pheromone molecule by the carboxyl radical reveals specificity of action of the used derivative: the frequency of disturbances revealed only by the ana-telophasic analysis increases, whereas by the metaphasic analysis, no induction of disturbance is detected. In the sperm head abnormality test there is shown a rise of the anomalies by both compounds.

[The role of metabolic activation of promutagens in the genome destabilization under pheromonal stress in the house mouse (Mus musculus)].

The hypothesis on a relationship between the high frequency of mitotic disturbances in bone marrow cells and the change in the activity of the S9 liver fraction containing promutagen-activating enzymes under olfactory stress in the house mouse Mus musculus has been tested. For this purpose, the effect of the pheromone 2,5-dimethylpyrazine on the frequency of mitotic disturbances in mouse bone marrow cells has been measured by the anaphase-telophase assay. The Ames test using Salmonella typhimurium has been employed to compare the capacities of the S9 liver fractions from stressed and intact mice for activating the promutagen 2-aminofluorene.

[Effects of "pheromone-like" pyrazine-containing substances on stability of genetic apparatus in bone marrow cells of the male house mouse (Mus musculus L.)].

There was studied effect of female house mouse pheromone 2,5-dimethylpyrazine and other pyrazine-containing substances on the genetic apparatus stability of dividing bone marrow cells of male mice of the strain CBA. Differences in action of the used chemosignals are revealed. Role of the method of action on induction of analyzed mitotic aberrations is shown.

[Effect of the estrous cycle stage on sensitivity to pheromone 2,5-dimethylpyrazine in the house mouse Mus musculus].

Frequency of cytogenetic disturbances was estimated in mitotically dividing bone marrow cells of CBA strain female mice after the 24-h long action of pheromone 2,5-dimethylpyrazine (2,5-DMP). The stage of the estrous cycle of each animal was taken into account at the moment of the end of the pheromone action. The analysis was performed using the anatelophase method that allows evaluating frequencies of various types of disturbances--bridges, fragments, delayed chromosomes.

[Stress, chemocommunication, and the physiological hypothesis of mutation].

The review considers stress as a physiological state of the organism, affecting the cellular, genomic, and population levels. Literature data and cytogenetic studies by the author support basic statements of the physiological hypothesis of mutation, which was advanced as early as in the 1940s. Studies of pheromonal effects in germline and somatic cells of the house mouse demonstrated the role of olfactory stressors in generating genetic variation in microevolutionary changes.

[Chromosomal abnormalities and spleenocyte production in laboratory mouse males after exposure to stress chemosignals].

Activity of antibody producing spleenocytes and chromosome stability in bone marrow cells from laboratory mouse males of CBA strain after exposure to different chemosignals excreted by stressed or irradiated syngeneic donors was studied. It has been shown that the exposure of the recipient males to volatiles from donor males (stressed by swimming) decreases quantity of antibody-producing cells in 1, 3 and 10 days after the treatment. The same exposure increased the chromosome aberrations level in dividing bone marrow cells from CBA recipients in 1 day after the treatment.

[Induction of meiotic disturbances in spermatocytes I by pheromones as an inhibiting mechanism of male reproductive function in house mice].

The influence of pheromons on reproduction and other important physiological characteristics has been reported for many mammalian species. However, mechanisms of this action at the level of target cells still remain unclear. A study was made of the influence of non-identified pheromones from adult males and a female pheromone 2,5-dimethylpyrazine on germ cells of CBA inbred strain mice.

[Induction of dominant lethals in progeny of male CBA mice after pheromonal action].

The inhibiting effect of pheromone 2,5-dimethylpyrazine of house mouse females on the reproductive function of the CBA male mice was studied. The mutagenic effect of six-day pheromonal effect was assessed by dominant lethal test. Analysis for the frequency of dominant lethals showed that the pheromonal effect results in an increased death rate of the progeny of the treated males.

[The female pheromone 2,5-dimethylpyrazine induces sperm head abnormalities in male CBA mice].

The effect of the house mouse female pheromone 2,5-dimethylpyrazine (2,5-DMP) on sperm differentiation in male CBA mice has been studied. For this purpose, mature males were treated with a 0.01% aqueous solution of the pheromone for six days.

[Analysis for pheromone-induced cytogenetic disturbances depending on major urinary proteins of male laboratory mice].

Young male CBA/LacStoRap mice for 2 h were exposed to pheromones that are transferred by major urinary proteins of sexually mature males of the same line. The treatment was conducted using either a complete set of the major urinary proteins typical of the CBA mice or incomplete set of protein fractions detected in some animals. The effect of pheromones was estimated 24 h after treatment by cytogenetic analysis for disturbances in dividing bone marrow cells at anaphase--telophase and in germ cells at metaphase I.

[Olfactory stress and modification of phagocytosis in peripheral blood cells of adult male mice].

Data on pheromonal influence on phagocytic activity of leukocytes in peripheral blood of adult randombred and CBA male mice have been obtained. The identified mouse pheromone 2,5-dimethylpyrazine was used, which induces some physiological effects associated with reproduction in both mouse males and females. Significant differences in spontaneous level of phagocytosis were between inbred CBA and randombred animals: the frequency of phagocytic cells was lower in CBA males by 1.

[Genotype-specific changes of certain functional indicators of immunocompetent cells in male laboratory mice under conditions of pheromone stress].

Mature laboratory male mice CBA, C57BL/6, BALB/c, and hybrids CBAB6F1 were exposed for 2 or 24 h to vapors of 2,5-dimethylpyrazine (DMP), which is a pheromone of the house mouse. This caused changes in the content of noradrenaline within the nerve fibers of both nasal mucosa and vascular testis tunic and an inhibition of leukocyte migration in the peripheral blood. Intrastrain distinctions were also revealed in the level of spontaneous leukocyte migration and intensity of the response to the DMP.

[Cytogenetic effect of volatile components of urine of sexually mature animals on bone marrow cells of young female house mice Mus musculus L].

Effects of volatile components of the urine (VCU) of mature male and female CBA/LacStoRap mice on proliferating bone marrow cells in young females of the same line were analyzed. To estimate the effects of VCU, cytogenetic analysis of mitotic disturbances in anaphase-telophase cells was performed. The overall frequency of mitotic disturbances such as chromosome bridges, fragments, retarded chromosomes, and multiple rearrangements was assessed.

[Cytogenetic effects of pheromones on bone marrow cells in male Mus musculus L. mice].

Young male CBA/LacStoRap mice were exposed for two hours to volatile components of native or dialyzed urine (VC or VCd, respectively) of mature males of the same line. To estimate the effects of VC and VCd on bone marrow cells, cytogenetic analysis of mitotic disturbances in anaphase-telophase cells was performed. The overall frequency of mitotic disturbances in VC-treated mice became significantly higher 24 and 48 h after exposure but returned to the initial level 72 h after exposure (P < 0.

Role of topoisomerase II in the structural and functional evolution of mitogen-stimulated lymphocyte nuclei.

To examine the role of DNA topoisomerase II (Topo II) in the mitogenic activation of mouse lymphocytes, we applied the Topo II inhibitor VM26 throughout the stimulation period and monitored morphological and functional parameters of lymphocyte activation. Cell viability and the usual increase in cell size were little affected at doses between 0.05 and 0.

[Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)].

A study of the influence of pheromone stressor(s) on proliferating germ and somatic cells was performed on laboratory lines of house mouse in the context of the physiological hypothesis of mutation process, proposed by M.E. Lobashev in 1947.

[Incidence of dominant lethals in the progeny of young male house mice (Mus musculus L.) after exposure to excretory products of mature males of the same species].

The influence of biologically active substances of excretory products (EP) of house mouse adult males on reproductive function of young males was studied with the help of the dominant lethal test. Mortality of the progeny and frequency of nonpregnant females were analysed on the 6th and 8th weeks after EP exposure. Preimplantation and postimplantation mortality frequency increased significantly (P less than 0.