Effects of chrysotile asbestos on DNA synthesis and growth of human embryonic lung fibroblasts.
The in vitro effects of asbestos fibers on thymidine (TdR3H) incorporation and growth of lung fibroblasts have been studied. Incubation of human embryonic lung fibroblasts with UICC Chrysotile B asbestos for 48 hr caused a 3 to 5-fold increase of TdR3H incorporation as compared with control cultures. This increase was dose-dependent with optimal effect obtained with doses as low as 10 micrograms/ml and with cell density of 5 X 10(4) fibroblasts per culture. However, enhanced TdR3H incorporation in treated cells was not correlated with an overall increase of the fibroblast population compared with control cultures as evidenced by cell counts and microscopic examination. Fibroblasts exposed to relatively low concentrations of UICC chrysotile (5-10 micrograms/ml) displayed an initial decrease in cell number compared to controls during the first 24 hr of incubation. At 48 hr however, enhanced TdR3H incorporation occurred with a concomittant increase in cell number. Moreover, continuous exposure of fibroblast cultures to chrysotile (10 micrograms/ml) for a longer period of time led to sustained increase of TdR3H incorporation and resumption of cell proliferation. It is suggested that increased thymidine incorporation is directly related to the effectiveness of asbestos in inhibiting the growth of lung fibroblasts and that measurement of TdR3H incorporation may represent a sensitive means of assessing rapidly the biological activity of asbestos. The possible relevance of this activity to asbestos-induced fibrogenesis and tumorigenesis is also discussed.
D001194:Asbestos / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011402:Pronase / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*
D001194:Asbestos; D004247:DNA; D011402:Pronase; D013936:Thymidine