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Journal of Pharmacology And Experimental Therapeutics, Vol. 104, Issue 1, 20-30, 1952
Copyright © 1952 by American Society for Pharmacology and Experimental Therapeutics

ADENINE INTOXICATION IN RELATION TO IN VIVO FORMATION AND DEPOSITION OF 2,8-DIOXYADENINE IN RENAL TUBULES

Frederick S. Philips 1, Aaron Bendich 1, and John B. Thiersch 2

1 Pharmacology and Protein Sections, Sloan-Kettering Institute for Cancer Research, New York
2 Department of Pathology, School of Medicine, University of Washington, Seattle

1. The toxicity of adenine has been studied in mice and rats. The purine was found to be nephrotoxic as the result of its in vivo oxidation to 2,8-dioxyadenine and deposition of the latter as crystalline occlusions in renal tubules.

2. The recovery of 2,8-dioxyadenine from kidneys has been studied in relation to dosage of adenine given rats. It was shown that renal deposition of the insoluble oxypurine occurred only after threshold amounts of the parent substance had been administered.

3. The toxicity of adenine was considered to bear no obvious relation to its ability to serve as a precursor of purines during biosynthesis of nucleic acids.

4. The manifold effects previously ascribed to adenine intoxication were considered herein to arise as secondary complications of uremia. It has also been suggested that adenine may be a dangerous agent for therapeutic use.

Submitted on August 10, 1951






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Copyright © 1952 by the American Society for Pharmacology and Experimental Therapeutics.