title: Effects of alpha-difluoromethylornithine on the growth of experimental Wilms' tumor and renal adenocarcinoma.
abstract: Because polyamines are essential for cellular growth and differentiation, and because human renal carcinomas have spermidine levels that are higher than those in normal renal tissue, effects of 2-difluoromethylornithine (DFMO) on the growth of experimental renal tumors were investigated. DFMO is a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme controlling polyamine biosynthesis. DFMO (2%) in drinking water was administered to BALB/c mice with intrarenal transplants of a renal adenocarcinoma cell suspension and to Wistar/Furth rats with s.c. transplants of a Wilms' tumor. At 28 days, renal carcinomas in DFMO-fed mice weighed 72% less than those in control animals (p less than 0.001). Wilms' tumor weight was not affected by DFMO feeding. DFMO caused 72 to 75% inactivation of ornithine decarboxylase activity and reduced putrescine levels in renal carcinoma and Wilms' tumor, reduced spermidine levels in Wilms' tumor, and apparently raised spermine levels in the latter as a consequence. DNA content was not affected by DFMO feeding. The mean number of lung metastases in DFMO-fed, renal carcinoma-bearing mice was 0.1 and in controls was 1.4 (p less than 0.001). DFMO feeding increased survival of mice bearing renal carcinomas by 3.0 +/- 0.8 (S.E.) days (p less than 0.05), i.e., from 30.5 +/- 0.8 days to 33.5 +/- 1.2 days. DFMO did not affect the growth of Wilms' tumor; however, in renal adenocarcinoma, it reduced growth, prevented lung metastases, and increased survival.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D000518:Eflornithine; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009952:Ornithine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D009396:Wilms Tumor / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D009952:Ornithine; D000518:Eflornithine