Effects Of Chrysotile Asbestos Research Articles

Молекулярные аспекты канцерогенеза, индуцированного асбестом

One of the key problems of modern healthcare is the prevention and personalized medicine of diseases caused by exposure to adverse environmental factors. According to the World Health Organization and the International Agency for Research on Cancer, all forms of asbestos have adverse effects on the human body and can induce various forms of cancer. It has been evidenced by the inclusion of asbestos in the first category of the list of carcinogens. Today the Republic of Kazakhstan is one of the largest asbestos-producing countries. An understanding of the key mechanisms of carcinogenesis due to inhalation of asbestos is needed to effectively diagnose asbestos-induced cancer in the early stages of development. The article reports on the most modern concepts of the genetic and molecular mechanisms of carcinogenesis mediated by the effect of chrysotile asbestos and confirms the danger of this compound to human health.

The Health Effects of Chrysotile Asbestos: Contribution of Science to Risk Management Decisions

The Health Effects of Chrysotile Asbestos: Contribution of Science to Risk Management Decisions

Remote effects in the mutagenic action of chrysotile asbestos and zeolite dustin vivo

It was proposed that there are a generalized mutagenic actions of chrysotile-asbestos fibers and zeolite particles in vivo. Chrysotile-asbestos fibers and different species zeolite particles in doses 50 mg/kg, intraperitoneally, increased the levels of damaged chromosomes not only in peritoneal cells, but also in bone marrow of C57BL/6 mice. Cytogenetic effect of chrysotile-asbestos does not depends on the time exposure of animals with mutagenic factor. In four weeks followed after administration chrysotile-asbestos fibers there were revealed 19-22% peritoneal cells with damaged chromosomes and 3.2-4.4% aberrant cells of bone marrow. Cytogenetic effect of zeolite particles was observed on 14-28 days after the administration, with peaks at 35.6% in peritoneal and 3.6-4.2% in bone marrow cells. Our data indicate the mutagenic action is realised as in cells contacted with dusts as in cells of other tissues. Probably, these effects are mediated by products of lipid peroxidation.

Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione- S-transferase activities in rat lung

The in vitro and in vivo effect of a carcinogenic variety of asbestos, chrysotile, both on xenobiotic metabolizing enzymes such as benzo[ a]pyrene hydroxylase, epoxide hydrolase as well as glutathione- S-transferase activities and microsomal lipid peroxidation in rat lung were examined. The in vitro incubation of chrysotile with microsomes significantly adsorbed heme proteins, cytochrome P-450 and P-448 with the concomitant decrease in the dependent monooxygenase activities. The prolonged incubation of this mineral fibre with microsomes also resulted in the release of heme. It also led to the depletion in the activities of epoxide hydrolase and glutathione- S-transferase. However, it induced lipid peroxidation. When these in vitro effects were validated in vivo, the exposure to early stages produced similar alterations as observed in in vitro studies. However, reverse pattern in the alterations was observed after 90 days of exposure except in the case of lipid peroxidation which remained induced.

Effects of chrysotile asbestos on coho salmon and green sunfish: Evidence of behavioral and pathological stress

The effects of chrysotile asbestos on larval coho salmon (Oncorhynchus kisutch) and juvenile green sunfish (Lepomis cyanellus) were investigated at levels approximating those reported in the Great Lakes basin (10(6) fibers/liter). Behavioral stress effects, such as loss of rheotaxic position and balance, were observed in salmon exposed at 3.0 X 10(6) fibers/liter and in sunfish exposed at 1.5 and 3.0 X 10(6) fibers/liter. Coho larvae at 1.5 X 10(6) fibers/liter were significantly more susceptible to an anesthetic stress test, becoming ataxic and losing equilibrium faster than control cohorts (P less than 0.001). Two of 106 larvae exposed at 3.0 X 10(6) fibers/liter developed tumorous swellings and three additional fish developed coelomic distentions. Cytological examination of ventral epidermal tissue revealed cellular histolysis, and evidence by transmission electron microscopy confirmed the presence of asbestos in the salmon larvae. Distortion of the lateral line region in asbestos-treated coho salmon was linked to behavioral and orientational aberrations. Differential mortality was not observed between control and treated groups of either test species.

Uptake of Chrysotile Asbestos Fibers Alters Growth and Reproduction of Asiatic Clams

The effects of chrysotile asbestos on siphoning activity, shell and tissue growth, fiber uptake, and gill ultrastructure in adult Asiatic clams (Corbicula sp.) and on larval release and mortality patterns from reproductively active adults were evaluated in 96-h to 30-d experiments at 0–108 fibers/L. Adult siphoning activity was significantly (α = 0.05) depressed in 96-h asbestos exposures when no food was offered or after 30 d when food was available. Shell growth was significantly inhibited in accordance with reduced siphoning. Corbicula exposed to 108 fibers/L accumulated 69.1 fibers/mg dry weight if food was offered. Fiber uptake was not observed at lower concentrations in 96-h or 30-d tests. Adult clams exposed to 108 fibers/L for 30 d accumulated 147.3 and 903.7 fibers/mg in gill and viscera, respectively. Gill tissue was significantly altered at 108 fibers/L and fibers were observed in gill locules and in ctenidial tissue. Fiber dimension analysis suggested that small, thin fibers were preferentially accumulated by both gill and visceral tissues. Significant increases in mortality of larvae exposed to asbestos and decreases in larvae released per milligram of adult dry weight were observed in reproductive adults exposed to asbestos at 104–108 fibers/L. Corbicula is an efficient accumulator of chrysotile asbestos and may be considered for use as an indicator of asbestos contamination.

Effect of Chrysotile Asbestos and Silica on the Microsomal Metabolism of Benzo(a)pyrene

Effect of Chrysotile Asbestos and Silica on the Microsomal Metabolism of Benzo(a)pyrene

Effect of chrysotile asbestos and silica on the microsomal metabolism of benzo(a)pyrene.

The effects of chrysotile, water-leached chrysotile, and silica on microsomal metabolism of benzo(a)pyrene in vitro were studied. Examination of benzo(a)pyrene metabolites generated by 3-methylcholanthrene-pretreated rat liver microsomes, in the presence of chrysotile fibers, revealed a reduction in the overall metabolism of the hydrocarbon. Thus, chrysotile appeared to modify the activities of aryl hydrocarbon hydroxylase and epoxide hydrolase. Leaching chrysotile in deionized water for 24 hr elicited a similar response. Silica, in contrast to chrysotile, did not decrease the microsomal metabolism of benzo(a)pyrene. Chrysotile, as well as water-leached chrysotile, considerably diminished the microsomal production of water-soluble benzo(a)pyrene metabolites. Precoating the fibers with heparin or bovine serum albumin partially abolished this inhibition. The liver microsomal metabolism of benzo(a)pyrene in rats subjected to intraperitoneal administration of chrysotile was 58% of that in untreated rats.

Effects of chrysotile asbestos on lung and pleural carcinogenesis of N-bis(2-hydroxypropyl)nitrosamine in rats

The effects of chrysotile asbestos on lung and pleural carcinogenesis by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in male Wistar rats were studied. Chrysotile, 30 mg per rat, was injected into the left pleural cavity and 3 g/kg body wt. DHPN was injected once into the abdominal cavity. Lung tumors (adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma) occurred at the highest incidence (100%). Adenocarcinoma was seen in 4 of 11 (36%) rats killed at 35 weeks and in 6 of 12 (50%) rats killed at 52 weeks, squamous cell carcinoma occurred in 1 of 11 (9%) rats killed at 35 weeks and 3 of 12 (25%) rats killed at 52 weeks, and mixed carcinoma was seen in 1 of 12 (8%) rats killed at 52 weeks, which received chrysotile and DHPN. Adenocarcinoma was seen in 9 of 11 (82%) rats which received DHPN only and killed at 52 weeks. Mesotheliomas were seen in 2 of 11 (18%) rats, killed at 35 weeks, and 3 of 12 (25%) rats, killed at 52 weeks, which received chrysotile and DHPN. Hyaline thickening of the pleura was seen in 100% of rats receiving chrysotile. Mesothelial cell hyperplasia and adenomatous and/or fibromatous growth of the mesothelium were seen in the pleura on both sides, ranging from 36% to 50% and 31% to 64% in rats receiving chrysotile and DHPN, respectively. Asbestos bodies were seen in the pleura on both sides and in the lung.

Effect of chrysotile asbestos (AP-I) on sister chromatid exchanges in Chinese hamster ovary cells

In vitro effect of an Indian variety of chrysotile asbestos from Andhra Pradesh (AP-I) is evaluated using sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Cultures were treated for 24 hr with different concentrations of asbestos fibers, i.e., 0.1, 1, 10, and 100 μg/ml of medium. Sister chromatid exchanges were elevated even with the lowest concentration used. However, the linear relationship between SCEs and asbestos concentration is not seen.

Two-Stage Carcinogenesis Studies With Asbestos in Fischer 344 Rats<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

The cocarcinogenic effect of chrysotile asbestos was investigated in heterotopic tracheal transplants of F344 rats. Tracheal transplants were first exposed to graded doses of dimethylbenz[a]anthracene (DMBA) contained in intraluminal pellets. The doses ranged from 12.5 to 100 micrograms. Control tracheas received blank pellets. Four weeks after the start of DMBA exposure (when all carcinogen had been released from the pellets), the spent pellets were removed, and 200 micrograms chrysotile, a nontumorigenic dose of asbestos, was introduced into the lumina of the preexposed tracheas. No significant enhancement of the tumor response was seen with 100 micrograms DMBA, a dose that was tumorigenic by itself. However, with 50 and 25 micrograms DMBA, nontumorigenic dose levels, a 15 and 23% incidence of tracheal carcinomas occurred when DMBA exposure was followed by a nontumorigenic dose of chrysotile. At 12.5 micrograms DMBA, this effect was not observed. Whatever the mechanisms were that formed the basis of this tumor enhancement effect of asbestos, the consequences were similar to those observed with tumor promotion in classical two-stage carcinogenesis studies.

Inhibition by phospholipids of haemolytic action of asbestos.

Haemolysis by asbestos fibres results from an increase in membrane permeability and not from rupture of red blood cells (RBC). The effect of chrysotile asbestos on RBC is at least partly, if not completely, attributable to lipid extraction and adsorption on to the fibres. This was suggested by the hyperbolic relationship between the haemolytic activity of chrysotile and the relative concentration of both chrysotile and RBC. Moreover, it was shown that pre-incubation of chrysotile with lipids, either as RBC membranes or with pure lipids in the form of liposomes, prevents haemolysis.

Light microscope studies on the effects of chrysotile asbestos and fiber glass on the morphology and reticulin formation of cultured lung fibroblasts

Chrysotile asbestos is highly cytotoxic when initially added to cultured lung fibroblasts, and this is reflected by cell death and by nuclear, nucleolar, and cytoplasmic abnormalities. Renewed growth and recovery of the culture occurs, but the subsequent deposition of reticulin is atypical. The results presented are correlated with earlier biochemical studies and subsequent electronmicroscopical investigations. Fiber glass causes little cell destruction, yet produces similar morphological changes but to a much lesser degree.