The effect of tumor burden on ornithine decarboxylase activity in mice.
Polyamines are essential for cell growth of normal and neoplastic tissue, alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor or ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. The purpose of this study was to examine the effects of tumor burden on ODC in tissues of tumor-bearing compared with tumor-free mice. Twenty-eight male Balb/c mice were divided into four groups of 7 each. Groups 1 and 2 were inoculated subcutaneously with 10 x 10(6) MC-26 mouse colon adenocarcinoma cells. Groups 3 and 4 were kept as tumor-free controls. Ten days after inoculation, groups 2 and 4 were injected with DFMO (200 mg/kg) intraperitoneally (IP) while Groups 1 and 3 received saline. Two hours after the injection of DFMO the animals were sacrificed. The tumor, pancreas, kidney, and liver were excised and analyzed for ODC activity. DFMO caused a significant reduction (compared with controls that did not receive DFMO) in the ODC activity of tumors; however, ODC activity of the kidney, pancreas, and liver of tumor-bearing mice was not affected. Additionally, the basal ODC activity in the kidney, liver, and pancreas of tumor-bearing mice was significantly lower compared with tumor-free controls. DFMO lowered ODC activity in the kidney, pancreas, and liver of tumor-free mice. These results suggest that the presence of MC-26 tumor causes systemic effects that alter ODC activity and the response to a known inhibitor of ODC.
Saydjari
R
R
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Alexander
R W
RW
Upp
J R
JR
Poston
G J
GJ
Barranco
S C
SC
Townsend
C M
CM
Thompson
J C
JC
D000818:Animals; D000518:Eflornithine / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D010179:Pancreas / Q000201:enzymology; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000473:pathology
D065108:Ornithine Decarboxylase Inhibitors; D009955:Ornithine Decarboxylase; D000518:Eflornithine