Effect of inhibitors of ornithine decarboxylase on retrovirus induced transformation of murine erythroid precursors in vitro.
alpha-Difluoromethylornithine (DFMO) and methyl acetylene putrescine (MAP) are inhibitors of the rate limiting enzyme in polyamine synthesis, ornithine decarboxylase. We studied the effects of these compounds on the formation of retrovirus transformed erythroid colonies. DFMO was able to effectively reduce the number of transformed colonies at a concentration of 10(-3) M, whereas MAP achieved total inhibition at 10(-4) M. Putrescine, the product of ornithine decarboxylase, did not alter colony number by itself but it was able to overcome the inhibitory effects of both DFMO and MAP. Addition of DFMO at times after the initiation of culture decreased its effectiveness in reducing transformed colony numbers, while the converse was true for the erythroid stimulant, erythropoietin. We concluded from these data that DFMO and MAP probably diminished colony formation by inhibiting proliferation of the target cells for the retroviruses.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D000518:Eflornithine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012190:Retroviridae
D065108:Ornithine Decarboxylase Inhibitors; D004921:Erythropoietin; D011700:Putrescine; D000518:Eflornithine