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6 Laboratory Studies of the Effects of Asbestiform Fibers
Pages 165-199

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From page 165...
... other asbestiform fibers exhibit pathogenic potential in animals. Lung Cancer ~.
From page 166...
... The development of lung cancers in rodents after inhalation of asbestos is specie~-specific. For example, rats and mice develop both benign and malignant neoplasms, whereas hamsters, guinea pigs, and rabbits develop only benign neoplasms (Botham and Holt, 1972a,b; Gardner, 1942; Gross et al., 1967; Reeves et al., 1974; Vorwald et al., 1951; Wagner, 1963~.
From page 167...
... from the USSR, brucite, and erionite. Fewer mesotheliomas occurred in rats after inhalation of UICC chrysotile, amosite, and crocidolite, but none appeared after inhalation of respirable fibrous glass, alumina, and ceramic aluminum silicate glass fibers.
From page 168...
... produced three mesotheliomas in 59 hamsters surviving 21 months or more. No such tumors were produced in guinea pigs and rats exposed to these fibers, or in smaller numbers of rats, guinea pigs, and hamsters inhaling amosite asbestos or ballimilled fiberglass (Lee et al., 1981~.
From page 169...
... 4. Other fibers evaluated in rodents by inhalation include alumina, which produced no fibrosis (Piggott et al., 1981~; PKT and Eybes, which caused fibrosis, but to a lesser extent than amosite (Lee et al., 1981~; and ceramic aluminum silicate glass, which induced alveolar proteinosis (Davis _ al., 1982~.
From page 170...
... The degree of hemolysis by particles, however, does not correlate directly with their fibrogenic or carcinogenic effects. The hemolytic activity of fibers relates to physicochemical properties such as size (Schnitzer and Pundsack, 1970)
From page 171...
... Because asbestos and other particles are believed to play a role in the pathogenesis of respiratory tract diseases, the mechanisms whereby these substances induce cytotoxicity have been investigated in cell culture (Chamberlain et al., 1982; Harington et al., 1975; Mossman et al., 1983a)
From page 172...
... Cell injury in tracheal epithelial cell cultures can be prevented by the addition of superoxide dismutase -- a scavenger of superoxide (Mossman and Landesman, 1983~. Cell death occurs rapidly when fibers are added to culture media without serum, hut is inhibited or delayed when serum is present (Harington et al., 1975; Mossman et al., 1980b)
From page 173...
... It is possible that cancers induced by asbestiform fibers result from the same fundamental mechanisms as cancers induces by other physical and chemical agents. Carcinogenesis is a complex, multistep process that has been extensively reviewed by Becker (1981)
From page 174...
... . Depending on the cell type, chemical tumor promoters can induce or inhibit normal differentiation (Diamond et al., 1978)
From page 175...
... , the V79-4 Chinese hamster lung cell line and cultured mesothelial cells did not exhibit altered SCE levels after exposure to crocidolite and chrysotile, respectively (Kaplan et al., 1980; Price-Jones et al., 1980~. Furthermore, in tracheal epithelial cells, chrysotile and crocidolite did not cause breakage of DNA, as measured by alkaline elusion (Mossman et al., 19836~.
From page 176...
... After exposure to amosite or crocidolite asbestos, there are increases in the incorporation of 3H-.chymidine (an indication of DNA synthesis) and basal cell hyperplasia in tracheal epithelial cells In vitro.
From page 177...
... is ingested by cultured mesothelial cells in both organ and monolayer cultures, whereas it is unclear whether larger fibers are phagocytized (Allison, 1973; Jaurand et al., 1979c ~ . After introduction into cultures of pleura, crocidolite causes proliferation of cells in a manner similar to that observed in tracheal organ cultures (Rajan et al., 1972~.
From page 178...
... . Additional evidence that asbestos acts as a promoter is provided by histological observations of hyperplasia and metaplasia in organ cultures of the respiratory tract after exposure to asbestiform fibers (Landesman and Mossman, 1982; Mossman and Craighead, 1974; Grossman et al., 19BOb; Woolworth et al., 1983a,b,c)
From page 179...
... . Taken together, these results are consistent with the hypothesis that certain asbestiform fibers may act in lung cancer in a manner similar to other known chemical and physical agents that have the properties of tumor promoters.
From page 180...
... . Again, the observations summarized above are similar to those reported for the mouse skin after exposure to chemical tumor promoters: infiltration of macrophages is observed, and hyperplasia and/or abnormal differentiation occurs in some cell types (Yuspa _ al., 1982~.
From page 181...
... Effects on immune system (e.g., activation of complement or chemotactic factors) aThe letters in this column represent diseases associated with exposure to f ibrou~ materials: A = Lung cancer B = Mesothe l ioma C= D = Fibrotic lung disease Gastrointe~tional tumors in this column represent the biologically relevant fiber 1 = Respirability (<3 Am diameter)
From page 182...
... However, since chemistry determines both durability and surface charge, the latter a feature directly related to cytotoxicity, chemistry may play at least an indirect role. Both inhalation and _ vitro studies indicate that asbestos is more pathogenic than a number of man-made mineral fibers (fibrous glass, glass wool, rock wool)
From page 183...
... A number of experiments are needed to relate the physicochemical features to biological effects. · In vitro and inhalation studies should be conducted to test whether the biological effects of asbestiform fibers are related to their size and shape.
From page 184...
... Results from these three types of studies should improve our understanding of the relationship between health effects and physicochemical properties of asbestiform fibers. This could lead to physicochemical modification of asbestos and related fibers to minimize their undesirable biological effects or, alternatively,to the synthesis of substitutes that possess the useful physicochemical properties of asbestos but that lack its known adverse health effects.
From page 185...
... 1981. Asbestos stimulates alveolar macrophages to release a factor causing hen lung fibroblasts to replicate.
From page 186...
... 1971. Epithelial outgrowths from lung tissue following intrapleural injection of asbestos dust in experimental animals.
From page 187...
... Presented at the Biological Effects of Man-Hade Mineral Fibers, Occupational Health Conference, Copenhagen, April 20, 1982. World Health Organization.
From page 188...
... 1967. Experimental asbestosis: The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust.
From page 189...
... 1978. Light and electron microscope studies of the rat digestive tract following prolonged and short-term ingestion of chrysotile asbestos.
From page 190...
... 1982. Induction of oraithine decarbosylase in hamster tracheal epithelial cells esposed to asbestos and 12-0-tetradecanoy} phorbol-13-acetate.
From page 191...
... 1983b. Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters.
From page 192...
... 1982. Comparative cocarcinogenic effects of crocidolite asbestos, hematite, kaolin, and carbon in implanted hamster tracheal organ cultures.
From page 193...
... 1983b. Effects of crocidolite and chrysotile asbestos on cellular uptake, metabolism and DNA after exposure of hamster tracheal epithelial cells to benzota~pyrene.
From page 194...
... Presented at the Biological Effects of Man-Made Mineral Fibers, Occupational Health Conference, Copenhagen, April 20, 1982. World Health Organizeeion.
From page 195...
... 1980. Interactions of chrysotile asbestos fibers with the complement system.
From page 196...
... Presented at the Biological Effects of Man-Made Mineral Fibers, Occupational Health Conference, Copenhagen, April 20, 1982. World Health Organization.
From page 197...
... lie To Vitro Effects of Mineral Dusts. Academic Press, New York.
From page 198...
... inoculation in rata. Presented at the Biological Effects of Manmade Mineral Fibers, Occupational Health Conference, Copenhagen, April 20, 1982.
From page 199...
... 1979. Biological activity of titanium dioxides.


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