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Decreased uptake of orotate in kidney tumors
Abstract:
The uptake of isotope by three transplanted kidney tumors after i.p. injection of 3H-labeled orotate was less than 5% of that in the host kidney cortex. A decrease of similar magnitude in the uptake into the acid-soluble tissue fractions from the kidney tumors was observed with very low incorporation into RNA relative to the host kidney cortex. Total uptake of orotate-3H and incorporation into RNA were several fold higher in the normal kidney cortex than in the kidney medulla and for the kidney cortex both parameters were less in young than in old rats. The uptake of uracil-3H by two kidney tumors was approximately 40% of that in the kidney cortex of host rats. Although the uptake of orotate-3H in kidney cortex was greater than that for uracil-3H the reverse situation was observed with kidney tumors, indicating that renal neoplasia in the rat is accompanied by an altered pattern of uptake of these metabolites.
Insights
Kidney tumors show significantly reduced uptake of orotate and uracil compared to normal kidney cortex in rats. This indicates altered metabolite uptake patterns in renal neoplasia.
Area of Science:
- Biochemistry
- Oncology
- Nephrology
Background:
- Kidney tumors exhibit distinct metabolic profiles compared to normal kidney tissue.
- Understanding the uptake of nucleobase precursors is crucial for cancer research.
Purpose of the Study:
- To investigate the uptake patterns of orotate and uracil in transplanted kidney tumors in rats.
- To compare metabolite uptake in tumor tissue versus normal kidney cortex and medulla.
Main Methods:
- Intraperitoneal injection of 3H-labeled orotate and uracil in rats with transplanted kidney tumors.
- Quantification of isotope uptake in tumor, kidney cortex, and kidney medulla tissue fractions.
- Analysis of incorporation into RNA and acid-soluble fractions.
Main Results:
- Kidney tumors showed less than 5% of the 3H-labeled orotate uptake observed in host kidney cortex.
- Orotate incorporation into RNA was significantly lower in kidney tumors compared to normal kidney cortex.
- Uracil-3H uptake in kidney tumors was approximately 40% of that in the kidney cortex, with orotate uptake showing the reverse trend.
- Orotate uptake and RNA incorporation were higher in kidney cortex than medulla, and decreased with age in rats.
Conclusions:
- Renal neoplasia in rats is associated with an altered pattern of orotate and uracil uptake.
- The reduced uptake of these metabolites in kidney tumors suggests potential differences in nucleotide biosynthesis pathways.