In vivo toxicity of phenothiazines to cells of a transplantable tumor.

The toxicities of three phenothiazines, promazine, chlorpromazine, and trifluoperazine, towards cells of a mouse fibrosarcoma were quantified by means of an in vitro assay of clonogenic cell survival. For all three drugs cell kill was proportional to the amount of drug injected. Following injection of equimolar (0.2 mM/kg) amounts, cell survival was progressively reduced for a period of at least 48 h. On the basis of cell survival at 48 h after administration the ranking of the drugs for cytotoxicity, in ascending order, was trifluoperazine, chlorpromazine, promazine. A period of acute hypoxia prior to processing of the tumor did not enhance the toxicity of any of the drugs, and no change in the size of the hypoxic fraction of the tumor was seen 24 h after the injection of chlorpromazine. On this basis it was concluded that there was no evidence of enhanced toxicity of drugs for either chronically or acutely hypoxic tumor cells. A reduction in the number of clonogenic tumor cells per gram of tumor was largely the result of a fall in the number of viable cells recovered from the tumor. The plating efficiency of surviving cells remained constant or was only slightly depressed.