[Carcinogenic and mutagenic activity of chrysotile, processed with iron chloride (III)].

This work is devoted to the study of the role of iron ions in the carcinogenic and mutagenic activity of chrysotile. For this aim natural chrysotile was treated with ferric chloride (III), washed, crushed and intratracheally introduced into Wistar rats. When administered to rats intact chrysotile induced mesotheliomas in 27,9 + 4,6% of cases, and chrysotile modified with ferric chloride - in 1,3 +/- 1,3%. Mutagenicity of the same samples was studied in the micronucleus test when administered intraperitoneally to mice Fl (CBA x S57Bl6). Polychromatic erythrocytes in the bone marrow were investigated 24 hours after intraperitoneal administration. The frequency of polychromatic erythrocytes with micronuclei was decreased from 7,4 +/- 0,18 by 1000 due to the action of chrysotile, from 2,8 +/- 0,42 for 1000 after the introduction of a modified sample. It is hypothesized that the ferric chloride modifies the surface of asbestos fibers that reduces the induction of free radicals which are the primary cause of and carcinogenic effects of chrysotile.

[Patterns of transposable elements distribution on the Drosophila melanogaster polytene chromosomes before and after selection for a quantitative trait].

The effect of selection for radius vein length on the distribution of hybridization sites of the P and hobo transposons and the mdgl and mdg2 retrotransposons on polytene chromosomes of Drosophila melanogaster salivary glands was studied. The patterns of these transposable elements (TEs) distribution were polymorphic in both the parental strain and selected strains. The similarity in mdg1 and mdg2 patterns between strains selected in one direction was closer than between strains selected in opposite directions, but the selected strains were closer to each other than to the parental strain regardless of selection direction. No mdg2 hybridization sites that would be absent in the control were found in the selected strains. There were more mdg2 and hobo hybridization sites in the strains selected in the (+) direction than in the (-) direction. The mobility of hobo copies in the strains studied correlated with the presence of its full-sized copy in the genome. The polymorphism of all TEs studied except for mdgl was greater for strains selected in the (+) direction that in the (-) direction. These facts suggest that some TEs migrate over the genome independently of selection, and others are markers of evolutionary events rather than their causes.

[Carcinogenic activity of the pesticide propoxur].

Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

[Change in the distribution of transposable elements in isogenic strain--cause or consequence in Drosophila melanogaster selection for quantitative traits?].

The distribution patterns pf hobo transposon and Dm412 retrotransposon hybridization sites on the salivary gland polytene chromosomes from the larvae of Drosophila melanogaster isogenic strain 51, used for analyzing the effect of transposable element (TE) transposition on the selection for quantitative traits, were studied, It was demonstrated that at least half Dm412 hybridization sites were retained 15 years after isogenization; the frequency of Dm412 transposition varied from 2.0 x 10(-4) to 8.8 x 10(-5) depending on whether the appearance of the same hybridization sites in some individuals were regarded as independent events or as a manifestation of the sample heterogeneity. The distribution patterns of hobo hybridization sites in two isofemale strains derived from isogenic strain 51 differed more noticeably: the number of hobo sites in one of the derivative strains was threefold smaller than in another and only a fraction of the sites was common. Within each derivative strain, the TE distribution was uniform, suggesting that inbreeding had no effect on the Dm412 activity in this strain. The rates of change in the distribution patterns of various TEs in strain 51 corresponded to their spontaneous transposition rates. As isogenic strain accumulates the polymorphism in TE distribution without selection, the TEs are more likely to be the markers of selection events than their inducers. Thus, when studying the effects of various environmental factors on TE transposition even in isogenic strains, it is necessary to perform rounds of close inbreeding to reduce the potential polymorphism.

[Experimental rationale for carcinogenic risk of asbestos cement industry and its products].

During intraperitoneal administration of dispersiveness-comparable chrysotile or asbestos cement fibers to rats (20 mg thrice), mesotheliomas were found in 45.1 and 7.7% of cases respectively. Asbestos cement dust induced tumors in 2.5% of cases, which is of biological importance. Cement or freeze asbestos destruction cement dust failed to cause tumors. The latter were not detected in a control group receiving physiological saline. Asbestos cement fibers and fascicles are covered by a cement matrix. Fiber amorphization gradually occurs. In lung tissue, there may be destruction of the cement coat of fascicles and release of native chrysotile fibers that are carcinogenic.

[Effect of peptone blocking asbestos-induced carcinogenesis in rats].

Regular intraperitoneal administration of peptone to rats was initiated immediately and 12 months after intraperitoneal thrice injection of crokidolite UICC in a dose of 20 mg. The rate of peritoneal mesotheliomas was 37.8% after co-administration of peptone and crokidolite, 25.6% following 12 months of crokidolite injection, and 72.1% after use of crokidolite alone. The effect of peptone administration is accounted for by the action of macrophages on transformed mesothelial cells and mesothelioma cells.

[Evaluation of the carcinogenic activity of phenol-free coal-tar creolin].

When orally administered to rats and mice, phenol-free coal-tar creolin containing 0.018+/-0.002 g/kg of benz(a)pyrene showed no carcinogenic activity. The discrepancy of the biological activity and content of carcinogen in the combined mixture, the role of their components in carcinogenesis, the value of control experiments, and historic control test, and the implication of these rapid tests in the evaluation of their carcinogenicity is shown.

[On decreasing carcinogenic activity of calcified chrysotile fibers].

When chrysotile fibers treated with Portland cement, Mg was partially substituted by Ca, therefore monolayer of Ca(OH)2 was formed as a cover, and that changed acidity force, number of active centers and biological activity (absent mutageneity, generation of active oxygen forms by macrophages was characterized by lower maximum and longer time to background level vs. native chrysotile).

[The response of the genomic pattern of transposable elements TE412 to quantitative trait selection in Drosophila melanogaster].

The results of four selection-genetic experiments aimed at the genetic transformation of the quantitative trait controlled by the radius incompletus gene of Drosophila melanogaster are given. Directional (s+) and (s-)-selection was conducted. At the of end all the experiments, in (s+)-selection the radial vein of the wing was restored to the wild phenotype, in (s-)-selection complete elimination of the radial vein took place. In four variants of selection, different TE412 pattern was formed under (s+)-selection and (s-)-selection in final generations. Correlation coefficient between (s+)-selection and (s-)-selection is -0.576, p < 0.001. At the same time, correlation coefficient between two independent replications of (s+)-selection is 0.912, p < 0.001, and of (s-)-selection, 0.946, p < 0.001. Thus, the availability of associated response to the selection of a quantitative trait and to the TE412 pattern is experimentally proved. Three hypotheses of the possible TE behaviour under selection are discussed.

[Impact of modification of the fiber surface of chrysotile on its biological activity].

Samples of commercial chrysotile-asbestos and asbestos cement, which were equal in number, were prepared. The content of fibers, up to 80 microm in length, was 87.4 and 85.0% in the first and second samples, respectively. Chemical analysis confirmed that there were cement components onto the surface of fibrils in the second sample. Onto the surface of native asbestos fibers, there were considerable distribution bands of active centers in the range of pH values of 5, 6.4, and 7.3; their largest number was at pH 6.4. Asbestos cement fibers had a band at pH 7.3, i.e. there was displacement towards the neutral region. Thus, their capacity for oxidative processes is likely to be lower than that in the fibers from the first sample. The mutagenic activity of the commercial chrysotile, examined in the micronucleus test, was substantially higher (p < 0.01) than that in the asbestos cement sample wherein it did not differ from that seen in the control experiment (saline solution). Mutagenicity was not found in cement and asbestos cement dust (2-3% of fibers) either. It is probable that the absence of mutagenicity in the cement-coated asbestos fibers may be attributable to a considerable reduction in their potencies for the formation of active radicals (oxygen, lipid peroxidation, and others).

[Characterization of the biological properties of acid-treated chrysotile-asbestos fibers].

Boiling of chrysotile of the textile brand PRZh1-50 in concentrated hydrochloric acid for 10, 15, and 20 minutes gave rise to three chrysotile-asbestos samples. The content of MgO decreased from to 24, 19, and 9%, respectively. As compared with the baseline values, the number and force of positively charged electrical centers were less in the samples containing 24 and 19% MgO and more in the sample having 9% MgO; the negatively charged centers were present in the former two samples and absent in the third one. When the samples were intrapleurally administered to rats, their hemolytic activity, induction of active oxygen radicals, mutagenic activity (micronuclear test using murine bone marrow cells), and the frequency of mesotheliomas were less in the treated samples than in the baseline ones; but there were no differences between the treated samples. Thus, the altered physicochemical properties of the fibrillar surface of asbestos diminished its biological aggressiveness; however, increased treatment rates failed to lead to its further decrease. There was no relationship of the biological properties to the number and force of electric charges of the surface.

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.

[Change in the system of wing venation of Drosophila melanogaster under heat shock and selection].

A change in the system of wing venation of Drosophila melanogaster appeared in response to heat shock and positive selection pressure directed to restoring the normal formation of wing radial vein, L2, that had been violated earlier by the recessive mutation of radius incompletes. Positive selection was effective, L2 having been formed correctly and completely to 35 generation. Besides, (+)-selection was accompanied by appearance of a small fragment of an additional vein at the wing tip. Selection directed to increase of size of this fragment resulted in the sufficient changes in the system of wing venation as a whole. It is suggested that, during evolution, transformation of wing venation of Drosophila was effected by the change of the way of prepattern realization, whereas the cells of wing plate continued to allow the formation of veins practically over a whole area.

[The effect of isogenization on the phenotypic manifestation of quantitative traits in Drosophila melanogaster]. / Vliianie izogenizatsii na fenotipicheskoe proiavlenie kolichestvennykh priznakov u 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.

[Analysis of the expression system of gene radius incompletes in Drosophila melanogaster]. / Analiz sistemy ékspressii gena radius incompletus u 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.

[Insignificant carcinogenicity of chrysotile asbestos of the Ak-Dovurak deposits in Russia and its possible links]. / Slabaia kantserogennost' khrizotil-asbesta Ak-Dovurakskogo mestorozhdeniia Rossii i ee vozmozhnye prichiny.

Thrice intrapleural injection of 20 mg of dust of the chrysotile from the Ak-Dovurak deposit caused pleural mesothelioma in 10.7% of the rats, which was significantly less than that upon exposure to the chrysotiles from other deposits and amphiboles. The reason for the less carcinogenicity of this chrysotile is the structural features of the surface of its fibrils, namely, its high homogeneity and hence the lack of sites at which the electrically charged centers may be located.

[The role of macrophages in asbestos-induced carcinogenesis]. / Makrofagi v asbestovom kantserogeneze.

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.

[Carcinogenic danger of zeolite from Kholinsk]. / Kantserogennaia bezopastnost' tseolita kholinskogo mestorozhdeniia.

The carcinogenic activity of the enterosorbent optisorb (pure zeolite) and the biologically active food additive litovite [zeolite and rye brans (1:1)] based on zeolite-clinoptololite from the Kholinsk deposit was studied. The intrapleural three-fold administration of optisorb (20 mg x 3) to rats and the inclusion of optisorb (5% of the feed) and litovite (5 and 0.06%) into the feed showed that these agents had no carcinogenic activity.

[Induction of MGE 412 transposition in an isogenic strain of Drosophila melanogaster by different doses of ethanol fumes]. / Induktsiia transpozitsii MGE 412 razlichnymi dozami parov étanola v izogennoi linii Drosophila melanogaster.

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.