Experimental chemotherapy in a transplantable renal adenocarcinoma. I: Effects of some inhibitors of polyamine synthesis.
Difluoromethylornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested for antitumor activity in the BALB/C mouse renal adenocarcinoma model, wherein ODC and AMDC activity are elevated compared to the normal kidney. Additionally, an indirect effector of AMDC synthesis, arabinofuranosyladenine and an inhibitor of AMDC synthesis, cycloleucin (CL), were tested in this model. Simultaneous administration of both DFMO and MGBG affected the growth of renal adenocarcinoma less than did administration of DFMO or MGBG alone. Combinations of inhibitors of polyamine synthesis demonstrated a high toxicity with low therapeutic activity. The most effective tumor suppression was observed with CL alone but associated toxicity was severe. Suramin, an ODC stimulator, may have enhanced tumor growth.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D000518:Eflornithine; D006146:Guanidines / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008935:Mitoguazone / Q000494:pharmacology / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011073:Polyamines / Q000096:biosynthesis*
D006146:Guanidines; D011073:Polyamines; D009952:Ornithine; D008935:Mitoguazone; D000518:Eflornithine