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

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Abstract
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.