Abstract
The aminonucleoside (PA) of puromycin is nephrotoxic to rats but not to guinea pigs. That guinea pigs are resistant to PA-nephrotoxicity has been confirmed in the Hartley strain. The metabolic disposition of subcutaneoulsy administered PA in the rat and in the Hartley guinea pig has been determined with the aid of the 8- 14C-labeled compound. Unchanged PA is the major urinary excretion product in both the rat and guinea pig 8 hr after PA administration, and allantoin represents the major end-product of metabolism. Guinea pigs, but not rats, excrete part of the PA-8- 14C as 14CO 2. The monodemethylated analog of PA, viz., 6-methylamino-9-(3′-amino-3′-deoxy-β- d-ribofuranosyl)purine, is the major nucleoside metabolite in the urine of rats and guinea pigs. The rat demethylates PA to this monodemethylated analog in vivo at a rate approximately 4-fold greater than the guinea pig.
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