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L N Pylev

Publications and source records attributed to L N Pylev.

At least 19 recordsLinked to original sources
PubMed2006

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.

Animals↗
PubMed2004

[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.

Animals↗
PubMed2002

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.

Animals↗
PubMed2002

[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.

Adult↗
PubMed2001

Inhibition of asbestos-induced transformation of rat pleural mesothelial cells in co-culture with rat macrophages.

The aim of this work was to investigate the influence of macrophages on the process of rat pleural mesothelium cells (RPMC) transformation in vitro. For this purpose prolonged many-passage co-cultivation of rat pleural mesothelial cells and rat peritoneal macrophages was performed both in the presence (to study macrophage influence on asbestos-induced morphologic transformation) and in the absence (to study spontaneous transformation) of asbestos. It was shown that spontaneous transformation of RPMC slightly accelerated in the co-cultures, whereas asbestos-induced transformation was strongly inhibited. For instance, RPMC acquired the ability to form multilayer cell growth foci and colonies in semisolid agar at 22-24 passages in the absence and at 14-16 passages in the presence of asbestos, while in co-culture with macrophages these signs of transformation appeared at 17-19 passages without asbestos treatment and were not observed at the 40th passage under exposure to asbestos. It was shown that the observed inhibition of transformation was caused by preferential depletion of transformed cells in co-cultures of mesothelium and macrophages in the presence of asbestos: when equal concentrations of macrophages and asbestos were taken, the viability of early-passage RPMC was greater as compared with late passages, and the viability of late-passage RPMC was greater than that of mesothelioma cells. The amount of late-passage RPMC and mesothelioma cells able to form colonies in semisolid media was also drastically decreased in these conditions. These findings suggest that though macrophages can influence the process of asbestos-induced mesothelium transformation by different ways, as a whole the inhibitory action appears to be the strongest.

Animals↗
PubMed2001

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.

Animals↗
PubMed2000

[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.

Animals↗
PubMed1999

Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations.

The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is frequently mutated in various tumors, human asbestos-associated MMs appear to develop independently from p53 alterations. The high mesotheliomagenic potency of natural fibrous mineral erionite is well established in humans and rodents, but no data regarding genetic alterations in erionite-associated tumors are currently available. Previous speculations that the oncogenic mechanisms underlying asbestos and erionite carcinogenesis may differ led us to examine whether the p53 gene is targeted in erionite carcinogenesis. Fifteen erionite-induced rat MMs as well as six cell lines derived from asbestos-induced and spontaneous rat MM were analyzed for p53 mutations by direct DNA sequencing and immunohistochemical analysis. Both approaches did not reveal p53 alterations in rat MM samples used in the study indicating that, similar to asbestos carcinogenesis, erionite carcinogenesis does not target the p53 tumor suppressor gene.

Animals↗
PubMed1998

Pathogenesis of experimentally induced asbestos mesothelioma in rats.

Fragments of parietal and visceral pleura were studied by total films preparation, light microscopy and SEM at different times after intrapleural injection of asbestos in Wistar rats. Pleural rat mesothelium in histological slices consists normally of one layer of oblong cells. By SEM the cells are flat and coated with microvilli of different lengths. In total films the parietal mesothelium was composed of large polygonal cells covering intercostal spaces and small cells covering spaces over the ribs. Inflammatory reaction and permanent pathological regenerative processes were observed in the mesothelium during 24 months after inoculation of asbestos fibres. Different lesions which we regarded as preneoplastic or premesotheliomatous were observed against the background of or without these processes. They were diffuse irregular hyperplasia and proliferation of epithelium-like or fibroblast-like cells and focal nodous proliferates composed of such cells with various morphological structures. The number of thymidine-labelled cells was significantly more inside the proliferates than in the surrounding tissue. They were confirmed by SEM and histological slices of the same fields. Chronic pathological regeneration of pleural mesothelium could be the background against which preneoplastic lesions and mesotheliomas develop easily.

Animals↗
PubMed1998

Spontaneous and asbestos-induced transformation of mesothelial cells in vitro.

The processes of spontaneous and asbestos-induced transformation of rat mesothelium were studied using cell cultures obtained in the laboratory. The same changes in cell properties were established in both spontaneous and asbestos-induced transformation: change in epidermal growth factor (EGF) response, in some cases appearance of fibroblast-like cells instead of polygonal ones, appearance of multilayer cell growth foci, and ability to grow in semisolid agar. The response to fibroblast growth factor, insulin-like growth factor 1, and insulin did not change during transformation as well as the P450 system activity measured by benz(a)pyrene (BP) and 7,12-dimethylbenzanthracene (DMBA) cytotoxicity. The asbestos-induced transformation began earlier than the spontaneous one. EGF began to stimulate mesothelium proliferation instead of its inhibition at 6-7 passages in the case of asbestos-induced transformation, whereas during spontaneous transformation this change began at 9-10 passages. Elongated rather than polygonal cells appeared at 10-11 instead of 17-18 passages (this morphological change did not take place at all lines studied). The ability to grow in semisolid agar was found at 14-16 passages with asbestos and at 22-24 passages without it. The results allow us to propose the necessity of a positive EGF response for mesothelial cell transformation and the similarity of mechanisms of spontaneous and asbestos-induced transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Characterization of the rat neurofibromatosis 2 gene and its involvement in asbestos-induced mesothelioma.

The neurofibromatosis 2 (NF2) tumor suppressor gene was recently implicated in the genesis of human mesothelioma. To investigate the role of this tumor suppressor gene in rat asbestos-induced mesothelioma, a commonly used model for the human disease, we characterized the rat homologue of NF2 and examined rat chrysotile-induced primary mesotheliomas and cell lines derived from chrysotile- and crocidolite-induced mesotheliomas for alterations in this gene. The coding sequence obtained for the rat NF2 gene had 90% nucleotide homology with the human NF2 gene. The rat NF2 gene was ubiquitously expressed as a 4.4-kb transcript in normal rat tissues as well as in rat mesothelioma cell lines. Reverse transcription-polymerase chain reaction analysis to examine splicing of NF2 exons in mesothelioma cells indicated that the exon splicing pattern was similar in normal and neoplastic cells. To determine if mutations had occurred in the NF2 coding region in rat mesotheliomas, single-strand conformation polymorphism analysis and direct sequencing were used to screen 10 primary tumors and six tumor cell lines. No DNA sequence alterations were observed in any of the rat mesothelioma samples examined. These findings contrast with data reported previously for human mesotheliomas, in which the NF2 gene was found to be mutated in 40% of cases. Taken together, these data suggest that the role of NF2 in the development of rodent asbestos-induced mesothelioma may differ significantly from the role in the human disease.

Animals↗
PubMed1996

[Experimental studies evaluating oncogenic effects of copper-nickel sulfide ore dust].

The experiments on animals studied mutagenic activity of copper-nickel sulfide ore dust. Micronucleus test proved mild mutagenic activity of the ore under study. Chronic inhalation of the dust induced malignancies (mostly lung tumors and leukoses) in 52% of the experimental Wistar rats, that could be caused by dissolution of the dust components in the body fluids.

Animals↗