Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the effect of diet.

This paper describes the development of a relatively rapid single-dose model for induction of lung adenomas in female A/J mice by the tobacco-specific nitrosamine 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK). Mice maintained on AIN-76A semi-synthetic diet were given a single i.p. dose of 2.5, 5 or 10 mumol NNK in saline and killed 3-7 months later. Maximum lung tumor induction, measured by lung tumors per mouse (tumor multiplicity), occurred in 3.5 months. There was no significant increase in tumor multiplicity between 3.5 and 7 months. Four months after treatment, numbers of lung tumors per mouse were 11.9 +/- 1.0 (10 mumol NNK), 3.6 +/- 0.4 (5 mumol), 0.9 +/- 0.4 (2.5 mumol) and 0.07 +/- 0.1 (saline). Lung tumor multiplicity in mice treated with a single dose of 10 mumol NNK and maintained on AIN-76A diet was significantly higher (8.3 +/- 0.5) than in mice treated with NNK and maintained on NIH-07 diet (2.5 +/- 0.3). The results of this study establish a useful bioassay for identification of compounds that can modify NNK-induced lung tumorigenesis.