Cytotoxic and cytogenetic effects of asbestos on human bronchial epithelial cells in culture.
Asbestos and other mineral fibers elicit responses in several rodent cell transformation systems. The mechanism of this transformation has been hypothesized to involve specific chromosome alterations, especially changes in chromosome number. However, the cytogenetic effects of asbestos fibers in cultured human respiratory epithelium have not been well characterized. The present study examined the effects of chrysotile and crocidolite asbestos fibers on cultures of human bronchial epithelial (HBE) cells growing in serum-free medium. HBE cells were continuously treated with chrysotile (0-4 micrograms/cm2) or crocidolite (0-300 micrograms/cm2) asbestos and examined after 24, 48, 72 or 96 h for cytotoxic and cytogenetic effects. Both asbestos fiber types induced a concentration-dependent inhibition of cell proliferation and colony-forming efficiency; however, in these assays chrysotile was 100-300 times more toxic than crocidolite. Concentrations of asbestos that inhibited growth had little effect upon trypan blue exclusion or intracellular esterase activity, suggesting that the majority of asbestos-exposed cells were still viable. A 2.7-fold increase in binuclei and a 1.6-fold increase in micronuclei were observed 72 h after treatment with 4 micrograms/cm2 chrysotile. A 1.9-fold increase in binuclei was observed 72 h after treatment with 300 micrograms/cm2 crocidolite, but crocidolite did not increase the incidence of micronuclei. Chrysotile asbestos failed to induce significant numerical chromosome changes in HBE cells and increased structural aberrations only at the 24 h time point. These findings contrast with the relatively high incidences of asbestos-induced chromosome changes previously observed in some rodent cell cultures and suggest the existence of species-specific or cell-type-specific differences in either chromosome stability or mechanism(s) of asbestos-induced toxicity.
Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
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Y
Kodama
C J
CJ
Boreiko
S C
SC
Maness
T W
TW
Hesterberg
D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite; D017632:Asbestos, Serpentine; D001980:Bronchi / Q000166:cytology* / Q000648:ultrastructure; D002455:Cell Division; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003114:Colony-Forming Units Assay; D006801:Humans; D015162:Micronucleus Tests
D017632:Asbestos, Serpentine; D017638:Asbestos, Crocidolite; D001194:Asbestos