Inhibition of cell growth and alteration of cytosolic calcium levels in the cytotoxicity evaluation of nine MEIC chemicals.
Inhibition of cell growth was compared in V79 and HeLa cell cultures treated for 60 hr with nine of the first 10 MEIC chemicals; FeSO(4) could not be tested because it produced artefacts. Whereas the IC(50) of digoxin was at least three orders of magnitude lower in HeLa cells, all the other chemicals were almost equally toxic in the two cell lines. The IC(50) values showed good correlation with the in vivo human toxic concentrations, but the correlation was better with HeLa cells, which allowed the species-related sensitivity to digoxin to be detected. The effects of acute exposures to the same compounds on the cytosolic free Ca(2+) of PC12 cells, a neurosecretory cell line derived from a rat phaeochromocytoma, were measured fluorometrically by the fura-2 method. Amitriptyline, methanol, ethanol and isopropanol increased resting [Ca(2+)](i), both in the presence of extracellular Ca(2+) and, to a lesser extent, in Ca(2+)-free medium. Diazepam, digoxin and ethylene glycol were effective exclusively in the former condition. The changes of resting [Ca(2+)](i) appear to be sensitive indicators of early cytotoxicity induced by different toxic chemicals.
Fortunati
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Department of Biology, Via Trieste 75, 35121 Padova, Italy; Department of Pharmacology, Largo E. Meneghetti 2, 35131 Padova, Italy.
Debetto
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Borella
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Bianchi
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