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The effect of tumor burden on ornithine decarboxylase activity in mice
R Saydjari1, R W Alexander, J R Upp
1Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Abstract:
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.
Insights
The study found that the presence of a tumor alters ornithine decarboxylase (ODC) activity in mice. Alpha-difluoromethylornithine (DFMO) effectively reduced ODC in tumors but not in other organs, suggesting systemic effects of the tumor.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Polyamines are crucial for cell proliferation in both normal and cancerous tissues.
- Alpha-difluoromethylornithine (DFMO) is a potent inhibitor of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis.
Purpose of the Study:
- To investigate how tumor burden influences ODC activity in various tissues.
- To assess the impact of DFMO on ODC activity in tumor-bearing versus tumor-free mice.
Main Methods:
- MC-26 colon adenocarcinoma cells were used to establish tumors in Balb/c mice.
- Mice were divided into tumor-bearing and tumor-free groups, with some receiving DFMO and others saline.
- ODC activity was measured in excised tumors, pancreas, kidney, and liver post-treatment.
Main Results:
- DFMO significantly reduced ODC activity in tumors compared to controls.
- Tumor-bearing mice exhibited lower basal ODC activity in the kidney, liver, and pancreas than tumor-free mice.
- DFMO administration did not affect ODC activity in the kidney, pancreas, or liver of tumor-bearing mice, but lowered it in tumor-free mice.
Conclusions:
- The presence of MC-26 tumors induces systemic changes affecting ODC activity.
- Tumor burden modifies the response of ODC to DFMO inhibition.
- These findings highlight complex interactions between tumors and host metabolism.