Lack of promoting effects from physical pulmonary collapse in a female A/J mouse lung tumor initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with remarkable mesothelial cell reactions in the thoracic cavity by the polymer

Experimental identification of potential chemopreventive or tumor promotive agents in the lung is important. Establishment of short-term bioassay models is therefore a high priority. In an attempt to induce strong promotion effects, in Experiment 1, left thoracotomy was performed on A/J mice at week 3 after initiation with 4-(methylnitrosamno)-1-(3-pyridyl)-1-butanone (NNK) (2 mg/0.1 ml saline/mouse i.p.) at weeks 0 and 1. In Experiment 2, at week 3, 0.2 ml of polymer gel was infused directly into the left cavity of the thorax with thoracotomy to occupy certain thoracic cavity volume and to examine the influence of physical pulmonary collapse. The experiments were terminated after 8, 10, 12 and 16 weeks in Experiment 1, and 12 weeks in Experiment 2 but no clear promotion effects in either experiment or pulmonary collapse due to infused polymer were apparent. However, a pronounced mesothelial cell reaction to the infused polymer was evident on the left lung surfaces and parietal pleura in Experiment 2. In conclusion, the present experiments did not demonstrate any clear lung tumor promotion effects of thoracotomy or physical left lung collapse. It remains possible, however, that alternative approaches might have greater efficacy and these need more consideration. In addition, mesothelial cells reaction was observed with the infused polymer.