Mitogenic activity of chloroform and carbon tetrachloride in serum-deficient or calcium-deficient cultures of human embryonic lung fibroblasts.
It was demonstrated that chloroform--studied in the non-toxic concentration interval 0.025-0.1% w/v--as well as carbon tetrachloride at 0.0125-0.05%, can support proliferation of cell cycling human embryonic lung fibroblasts in Dulbecco's modified Eagle's medium (DMEM) complemented with 0.5% foetal calf serum. This serum concentration restricts the growth of the non-solvent treated fibroblast (control) cultures. Even after a pretreatment of the fibroblasts with the low serum-medium for up to 4 days, the cells responded to the mitogenic impulse of the solvents. This indicates that quiescent fibroblasts are also sensitive to the mitosis-stimulating effect of the solvents. The effect of the solvents in serum-free DMEM was followed in a short-term study in order to determine if cofactor(s) from serum are needed for expression of the mitosis-stimulating activity of the solvents. Carbon tetrachloride was shown to be mitogenic for the fibroblasts. At solvent concentrations greater than or equal to 0.00078% w/v the cells were observed to proliferate about as rapidly as control cells incubated in 10% serum-containing DMEM. After change from solvent-containing to solvent-free medium cell proliferation was soon inhibited. Chloroform was not mitogenic in the serum-free medium. The mitogenic activity of CHCl3 or CCl4 in solvent containing 10% serum and reduced content of calcium ions (0.05 mM) was then determined. It was shown that the solvents under the non-physiological conditions support proliferation of the fibroblasts for 2-3 days depending on the solvent concentration.
Brunius
G
G
Department of Toxicology, National Institute of Occupational Health, Solna, Sweden.
D001790:Blood Physiological Phenomena; D002118:Calcium / Q000502:physiology*; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002725:Chloroform / Q000494:pharmacology*; D003470:Culture Media; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology; D008934:Mitogens; D013482:Superoxide Dismutase / Q000494:pharmacology
D003470:Culture Media; D008934:Mitogens; D002725:Chloroform; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D002118:Calcium