A quantitative metabolic inhibition test for screening toxic compounds with cultured cells.
The toxicity of substances for monolayer cultures of rat lung fibroblasts with phenol red as a pH indicator in the medium was measured by comparing the changes produced in medium color against 10 stable color standards. The toxicities of 6 concentrations each of actinomycin D, amphotericin B, chloroquine, 2-deoxyglucose, oligomycin, puromycin, and silicon dioxide were measured at 12 h and daily for 7 days on the same cultures throughout. Morphologic changes were monitored at the same times. The method, which simultaneously measures both concentration and time effects, was rapid, simple-to-perform, reproducible, low-in-cost, and quite sensitive. Its reproducibility depended on details of the cell culture methodology. The method is unsuitable for acidic or basic substances, or substances poorly-soluble in culture medium. Unless combined with morphologic evaluation, substances producing delayed toxicity may give misleading results.
D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000187:drug effects; D051381:Rats; D014116:Toxicology