Toxicity to HeLa cell of 205 drugs as determined by the metabolic inhibition test supplemented by microscopy.
The toxicity of 205 drugs to HeLa cells was evaluated by the Metabolic Inhibition Test supplemented by microscopy. Two end points of cyto-inhibition were estimated; total and partial inhibition after 24 h, based on absence or scarcity of spindle-shaped cells, respectively, and total and partial inhibition after 7 days, based on different degrees of basic pH change of the phenol red included in the cell medium. Direct drug-induced pH changes and precipitates in the cultures were also recorded. Many drugs were found to induce a culture zone with a particularly low pH after 7 days of incubation, at concentrations below the cyto-inhibitory concentration. Forty-three drugs regularly caused this hyperacid reaction, while 44 drugs caused the reaction irregularly. Since the reaction was always continuous with the cyto-inhibitory zone, it was provisionally judged to represent excitatory cell injury. Since many of the drugs which regularly induced the reaction are also known to induce proliferation of the endoplasmic reticulum in various cells, the reaction may be related to this and allied effects. Many drugs that are known to accumulate in cells displayed a high inhibitory toxicity, which might have been due to the paucity of cells in the test system. However, the high 7-day inhibitory toxicity shown by antineoplastic and some anti-inflammatory drugs, including triamterene and disulfiram, may constitute a genuine antimetabolic drug action. Seven grand mal antiepileptics were only very slightly toxic as compared with their precipitating tendency, which may be of significance in their therapeutic action.
D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008853:Microscopy; D012997:Solvents; D014116:Toxicology
D012997:Solvents