A study of tobacco carcinogenesis XLIV. Bioassay in A/J mice of some N-nitrosamines.

The evaluation of the tumorigenic activity in A/J mouse lung of certain tobacco N-nitrosamines, namely 3-(methylnitrosamino)propionic acid (NMPA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-4-(3-pyridyl)-butyric acid (iso-NNAC), had the following results (total dose in micromol per mouse/lung tumors per mouse): NMPA (200/7.1 +/- 2.9); NNK (2/15.7 +/- 4.1); iso-NNAC (200/0.24 +/- 0.43); saline control (0.2 +/- 0.4). The tumorigenic activity of NMPA was not surprising since its lower homologue, N-nitrososarcosine, as well as its higher homologue, 4-(methylnitrosamino)-butyric acid, are known carcinogens. The high tumorigenic activity of NNK in strain A/J mice confirms earlier findings as to its carcinogenic potency in rats and hamsters. The lack of tumorigenic activity of iso-NNAC supports the observation that the pyridyl rest adjacent to the nitrosamino group inhibits the activity of some tobacco-specific N-nitrosamines (TSNA). Iso-NNAC is most likely formed endogenously from the nicotine metabolites cotinine and 4-(methylamino)-4-(3-pyridyl)butyric acid.