[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.

[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). The mechanisms and importance of the revealed antimutagenic effect of mouse female chemosignals on the male reproductive cells in the reproduction process 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. Preliminary 24-h-long action of chemosignals of isolated females decreases effect of the subsequent action of 2,5-dimethylpyrazine, although the level of disturbances exceeds that in control animals. The simultaneous action of used chemosignals neutralizes completely the 2,5-dimethylpyrazine action, the frequency of mitotic disturbances being not different from that after chemosignals of isolated females. The hypothesis is put forward about dependence of the revealed cytogenetic effects in male recipients on zoosocial conditions of maintenance of female donors of chemocommunication signals.

[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. Possible mechanisms of specific action of the tested substances on stability of genetic apparatus of the bone marrow dividing cells in the house mouse are discussed.

[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. It has been demonstrated that the increased frequency of mitotic disturbances in bone marrow cells induced by the pheromonal stressor in male house mice is accompanied by an increased promutagen-activating capacity of the S9 liver fraction. The model system used in the study allowed the genetic consequences of the exposure to the olfactory stressor to be estimated and the possible mechanisms of genome destabilization to be assumed.

[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. Spectrum of the aberrations is analyzed. Dependence of cytogenetic activity of the used substances on their structural peculiarities and significance of the revealed effects are discussed.

[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. Similar changes were observed in 24 h after exposure to volatiles of irradiated donors or to synthetic mouse pheromone, 2,5-dimethylpyrazine. Possible mechanisms of chemosignals effect on the immune system are discussed.

[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. The spontaneous level of the mitotic disturbances revealed by the anatelophase method in animals of the control group amounts to 5.4 %. Action of pheromone 2,5-dimethylpyrasine induced the mitosis disturbances detected in the dividing bone marrow cells at the anaphase-telophase stage in the females at the di- + postestrus stage. The corresponding frequency of disturbances after the pheromone action was equal to 9.2%. In the female in estrus, the mitotic disturbance level amounted 6.7%, which did not differ statistically significantly from control. It is suggested that differences in the female mouse hormonal state at different estrous cycle stages affect sensitivity to olfactory signals. Mechanisms of the revealed effect and significance of the differences in sensitivity to pheromone for reproductive processes are discussed.

[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. Cytogenetic analysis shows a significant increase in such meiotic disturbances as multivalent associations and autsomal univalents 24 h after exposure to pheromonal cues. Results of in situ hybridization show that the level of c-fos and c-jun expression is significantly higher 3.5 h after exposure to pheromones of adult males. It is likely that destabilization of chromosomal apparatus in dividing meiotic cells forms the basis of some reproductive effects of murine pheromones. Possible mechanisms of pheromone influence on reproduction are discussed.

[Induction of dominant lethals in progeny of male CBA mice after pheromonal action]. / Induktsiia dominantnykh letalei v potomstve samtsov myshei linii SBA posle feromonal'nogo vozdeistviia.

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. This is probably explained by implantation failure and is expressed in a reduced average number of the implantation sites and low live embryos per female. The proportion of females with live embryos decreased significantly. The implication of the effect of female mouse pheromone 2,5-dimethylpyrazine on the genetic processes in germ cells of male mice is discussed.

[The female pheromone 2,5-dimethylpyrazine induces sperm head abnormalities in male CBA mice]. / Induktsiia anomalii golovok spermiev u samtsov myshei linii CBA feromonom samok myshei 2,5-dimetilpirazinom.

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. Control mice were similarly treated with physiologic saline. The mice were sacrificed 23 days after the treatment, and material for the analysis of sperm-head abnormalities was sampled from the caudal portion of the epididymis. Analysis of the frequency of abnormal sperms has demonstrated that the pheromonal treatment significantly increases the frequencies of various sperm-head abnormalities. Apparently, this results from disturbances in sex-cell differentiation germline cells caused by the induction of genetic damage at stages immediately preceding meiosis, as well as during the first and second meiotic divisions. The relationship between the effect of 2,5-DMP and the decrease in the fertility of male CBA mice that was earlier observed after a similar treatment is discussed.

[Analysis for pheromone-induced cytogenetic disturbances depending on major urinary proteins of male laboratory mice]. / Izuchenie feromonal'noi induktsii tsitogeneticheskikh narushenii v zavisimosti ot sostava glavnykh belkov mochi u samtsov laboratornykh myshei.

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. The frequency of both mitotic and meiotic disturbances was significantly increased after exposure to pheromones associated with the complete spectrum of the major urinary proteins. Conversely, no cytogenetic effect was observed in the absence of particular protein fractions. Possible consequences of the pheromonal effect on the genomes of somatic and germ cells are discussed as well as the relationships between pheromones and the major urinary proteins.

[Olfactory stress and modification of phagocytosis in peripheral blood cells of adult male mice]. / Ol'faktornyi stress i modifikatsiia fagotsitoza v kletkakh perifericheskoi krovi polovozrelykh samtsov myshei.

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 1.4 times. The substance tested here induces phagocytosis in randombred (by 1.7 times) males. A low dose of 2,5-dimethylpyrazine (similar to the natural pheromone concentration) induces a higher increase in phagocytic activity by leukocytes. Possible mechanisms of pheromonal action on phagocytosis are discussed with the perspectives of finding highly effective immunomodulators among mammalian pheromones.

[Genotype-specific changes of certain functional indicators of immunocompetent cells in male laboratory mice under conditions of pheromone stress]. / Genotipspetsificheskie izmeneniia nekotorykh funktsional'nykh pokazatelei immunokompetentnykh kletok u samtsov laboratornykh myshei v usloviiakh fermonal'nogo stressa.

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. The mechanisms underlying these effects and their possible adaptive significance are discussed.

[Cytogenetic effect of volatile components of urine of sexually mature animals on bone marrow cells of young female house mice Mus musculus L]. / Tsitogeneticheskii éffekt deistviia letuchikh komponentov mochi polovozrelykh zhivotnykh na kletkakh kostnogo mozga molodykh samok u domovoi myshi (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. The overall frequency of mitotic disturbances in young female mice treated with VCU from mature females for 2 h significantly increased 24 h after exposure. The spectrum of mitotic disturbances was also affected by the VCU treatment. After exposure to VCU from mature males, no significant variation of parameters analyzed was detected in young female mice. The possible mechanisms and role of specific effects of VCU from animals of different sexes on young female house mice are discussed.

[Cytogenetic effects of pheromones on bone marrow cells in male Mus musculus L. mice]. / Tsitogeneticheskie éffekty feromonov v kletkakh kostnogo mozga u samtsov domovoi myshi Mus musculus L.

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 < 0.05). Similar effects were observed after 24 h in mice exposed to VCd. These results suggest that VC and VCd are capable of disturbing the stability of genetic processes in proliferating bone marrow cells. Evidence was also obtained that these components are associated with major urinary proteins. The significance and possible mechanisms of effects observed in the study are discussed.

[Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)]. / Feromonal'nyi kontrol' geneticheskikh protsessov: issledovaniia na domovoi myshi (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. Data from experiments are presented, and results obtained during last 10-15 years are discussed. The adaptive role of cytogenetic and other observed pheromonal effects is considered. The possible existence of interorganism systems of genetic regulation is discussed, the search for and study of which may help in more complete understanding of the regularities of functioning of genetic material.