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Metabolic Fate of Nitrosoproline in the Rat¹

Fels Research Institute [C. C., P. N. M.] and Department of Pathology [P. N. M.], Temple University School of Medicine, Philadelphia, Pennsylvania 19140

The metabolism of [U¹⁴C]nitrosoproline and [carboxyl-¹⁴C]nitrosoproline was studied in the rat. In most experiments, less than 1% of the administered radioactivity appeared as radioactive CO₂ in the expired air, and urinary excretion of radioactivity was rapid and almost complete as the unchanged compound, which was the only radioactive component detected in the urine. The absence of any radioactive urinary components corresponding to proline or its metabolites indicated that no detectable metabolic denitrosation had occurred. Studies of the disappearance of nitrosoproline from the circulating plasma indicated an apparent volume of distribution of 52% of the total body weight, suggesting some penetration by the compound into the intracellular space. There was no significantly detectable covalent binding of radioactivity from the labeled nitrosoproline to DNA or RNA of the liver and only an extremely low level of binding to liver protein. Taken with the reported noncarcinogenicity of nitrosoproline in rodents, the above findings suggest that proline may be a suitable nitrosatable substrate for use in tests of endogenous nitrosation reactions in animals and human subjects.

¹ This research was supported by Grants CA 12227 and CA 23451 from the National Cancer Institute, NIH, and by the Samuel S. Fels Fund of Philadelphia.

² To whom requests for reprints should be addressed.

Received 3/31/81. Accepted 6/17/81.