[The effect of treatment of chrysotile with chloride iron (III) on the effect of genomic instability in cultured human lymphocytes].

All forms of asbestos are carcinogenic to humans, that caused the prohibition of its use in Europe, America, etc. However, the unique physical and chemical properties of asbestos and many opportunities for its applications in various industries and human activities require the creation of new technologies to. Analysis of genomic instability in human lymphocytes in a large range of doses (micronucleus test with cytochalasin B showed a decline of core indicators of genome instability (frequency of dividing cells with cytogenetic damage, asymmetry in the distribution of the genetic material in mitosis, proliferative activity) incubation of cells with asbestos modified chloride iron, as compared to the initial sample. These data are consistent with the results of analysis of the intensity of neutrophil chemiluminescence of luminol by exposure of human blood samples studied. Based on the findings made some practical recommendations to the protocol cytogenetic analysis of genomic instability of people exposed to asbestos.

[Chrysotile-asbestos induces cytogenetic effects in the rat's mesothelium in vitro and in vivo].

Under cultivation of rat peritoneal mesothelial cells in vitro in them there are appeared signs of the genomic instability, evidencing their transformation: increasing of the number of both binucleated cells with micronuclei and polynuclear cells and the increase of sizes and polymorphism. Asbestos greatly accelerates this process. Asbestos-induced carcinogenesis in vivo is accompanied in pleural mesothelium in the rats there also revealed with similar signs of genomic instability and cellular transformation.

[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.

[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.

[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).

[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.

[Carcinogen activity of the new drug thymodepressin studied in chronic tests on rats and mice]. / Izuchenie kantserogennoi aktivnosti novogo lekarstvennogo sredstva - timodepressina v chronicheskikh opytakh na krysakh i myshakh.

The new drug thymodepressin was subcutaneously injected in doses 0.0145 and 0.145 mg/kg in rats and mice over a period of 104 weeks. No statistically significant difference in the tumor frequencies between the test and control groups was observed during this period of time. It is concluded that thymodepressin is not carcinogenic.

[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.

[The electric properties of fiber surface and the toxicity of asbestos]. / Elektricheskie svoistva poverkhnosti volokon i toksichnosti asbesta.

Thermal treatment, autoclaving and their combination yielded 3 samples of chrysotile-asbestos. With these, as compared with parent Type PRZh-1-50 Bazhenov chrysotile, the structure of fibers deteriorated and the number of negative discharges increased in the first two samples; the superficial structure substantially increased and the number of positive centers greatly decreased in the third sample. The ratio of positive to negative centers was less in all treated samples than that in the parent one, it decreased particularly during combined treatment. In this sample, hemolytic and mutagenic activity and cytotoxicity were substantially decreased; carcinogenic activity was greatly decreased (by 4 times) (as shown by the pleural mesothelioma indication test during intrapleural administration to rats). Thermal treatment and autoclaving insignificantly lowered the hemolytic activity and mutagenicity; carcinogenicity of these samples was much less (by 2.3 and 2 times) than that of parent chrysotile.

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.

[On carcinogenic effects of sulfate copper and nickel ore]. / Ob onkogennom deistvii pyli sul'fidnykh medno-nikelevykh rud.

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.