Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosainino)-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 ip. dose of 2.5, 5 or 10 μmol 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 μmol NNK), 3.6 ± 0.4 (5 μmol), 0.9 ± 0.4 (2.5 μmol) and 0.07 ± 0.1 (saline). Lung tumor multiplicity in mice treated with a single dose of 10 μmol 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 identifi cation of compounds that can modify NM lung tuinorigenesis.