EFFECTS OF INTRALESIONAL INJECTION OF CISPLATIN DISSOLVED IN UROGRAFIN AND LIPIODOL ON EHRLICH ASCITES TUMOR AND NORMAL-TISSUES OF CD-1 MICE

The response of Ehrlich ascites tumor and the effect on normal tissues (kidney and small intestine) of CD-1 mice were evaluated after intral esional (i. 1.) injection of cisplatin dissolved in urografin and lipi odol, which is henceforth termed CUL suspension. The results obtained were compared with the effects of i. p. and i.1. injections of cisplat in dissolved in sterile distilled water. Each of these treatment modal ities involves the injection of 10 mg/kg cisplatin. The tumor response was evaluated by tumor growth-delay studies as well as by determining the percentage of cells in the S phase. Toxicity studies were accompl ished by evaluation of the change in the body weight of mice and also by S-phase studies. S-phase fraction analyses were done with the use o f the Cell Proliferation Kit. This commercial kit was used to measure bromodeoxyuridine (BrdU), a thymidine analogue that is incorporated in to cells synthesizing DNA. Tumor, kidney, and small-intestine platinum concentrations were determined by measurement with a flameless atomic absorption spectrophotometer. The results of the tumor growth-delay s tudies showed that i. p. injection, with water being the drug carrier, produced the weakest antitumor effect, whereas i.1. injection of cisp latin, with lipiodol being the drug carrier, evoked the most enhanced effect. This finding was substantiated by BrdU-uptake analysis of tumo r cells, wherein i.p. injections yielded the highest S-phase fraction and CUL treatment gave the lowest. Toxicity studies showed that a very significant decrease in body weight occurred in mice receiving i.p. t reatment. No significant decrease in body weight was noted after i.1. treatment. BrdU analysis revealed that DNA synthesis in kidney cells a nd crypt cells of the small intestine was depressed after i. p. treatm ent. On the other hand, no significant effect was observed in the kidn ey or small intestine of CUL-treated mice. A correlation between the e ffects of the various treatment modalities (on tumors, kidney, and sma ll intestine) and the retention of cisplatin was found.