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Dose-Response Study of N-Nitrosoproline Formation in Rats and a Deduced Kinetic Model for Predicting Carcinogenic Effects Caused by Endogenous Nitrosation¹

International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon Cedex 8, France

A dose-response study on the endogenous formation of N-nitrosoproline in rats was carried out by feeding various doses of L-proline in the diet and sodium nitrite in the drinking water. N-Nitrosoproline excreted in the urine and feces of individual rats was monitored as an index for endogenous nitrosation of proline.

The logarithm of the amount of N-nitrosoproline formed was found to be proportional to the logarithm of the product of the proline dose and the square of the nitrite dose, in agreement with in vitro studies. On the basis of these results, a kinetic model was formulated. Calculations were carried out with this model using published data on nitrosation and carcinogenic potency of selected N-nitrosamines. This allowed the estimation of the daily precursor dose quantity, [amine][nitrite]², required to give 50% tumor incidence in rats after 2 years of feeding.

¹ The TEA detector used in this study was provided on loan by the National Cancer Institute, Bethesda, Md., under Contract NOI CP-55717.

² Visiting scientist at the International Agency for Research on Cancer under a CEC scientific and technical grant.

³ To whom requests for reprints should be addressed.

Received 2/23/83. Accepted 7/29/83.