Dose-response study of N-nitrosoproline formation in rats and a deduced kinetic model for predicting carcinogenic effects caused by endogenous nitrosation.
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.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000032:analysis; D007700:Kinetics; D009573:Nitrites / Q000633:toxicity*; D009602:Nitrosamines / Q000378:metabolism* / Q000652:urine; D011392:Proline / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D012977:Sodium Nitrite / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D009573:Nitrites; D009602:Nitrosamines; D011392:Proline; C010259:nitrosoproline; D012977:Sodium Nitrite