In vitro assays to predict the pathogenicity of mineral fibers.
A number of mineral dusts are associated with the development of inflammation in lung and pulmonary interstitial fibrosis. In an effort to find alternative approaches to animal testing, cells (rat alveolar macrophages, hamster tracheal epithelial cells, rat lung fibroblasts) of the respiratory tract have been evaluated for cytotoxic and metabolic changes after exposure to fibers (defined as a greater than 3:1 length to diameter ratio) and particles. In all bioassays, fibrous materials provoked greater biological responses in cells in comparison to non-fibrous, chemically similar particulates at identical concentrations. For example, release of superoxide (O2-.) from alveolar macrophages (AMs) was increased (in comparison to that observed in untreated cells) after exposure to the fibers, crocidolite asbestos, erionite, Code 100 fiberglass and sepiolite. Riebeckite, mordenite and glass particles elicited minimal generation of O2-. at similar concentrations of dusts. In hamster tracheal epithelial (HTE) cells, fibers such as chrysotile asbestos, crocidolite asbestos, and Code 100 fiberglass caused increased release of 51Chromium in comparison to the particles antigorite, riebeckite and glass. Another area of exploration is the measurement of collagen and non-collagen protein in a cell line (RL-82) of rat lung fibroblasts as an indication of the fibrogenic potential of minerals. Crocidolite asbestos caused an increase in the ratio of cell-associated collagen to non-collagen protein in these cell types whereas glass beads did not affect biosynthesis of collagen. Results suggest that a battery of in vitro assays can be used to screen the capability of minerals to elicit cell damage and inflammatory changes in the respiratory tract.
Mossman
B T
BT
Department of Pathology, University of Vermont College of Medicine, Burlington 05405.
Sesko
A M
AM
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D017632:Asbestos, Serpentine; D002460:Cell Line; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004391:Dust / Q000009:adverse effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008903:Minerals / Q000633:toxicity*; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013481:Superoxides / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D017632:Asbestos, Serpentine; D004391:Dust; D008903:Minerals; D013481:Superoxides; D001194:Asbestos; D003094:Collagen