Abstract 343: Transgenic C57/BL6 x Balb/c F1 mice expressing mitochondrial targeted catalase have less spontaneous lung cancer.

Abstract

Abstract Human lung cancer is a major cause of morbidity and among the most frequent and deadly malignancies throughout the world. Discrepancies in classification and characterization approaches have resulted in confusions and difficulties in the comparative pathology of mouse and human lung tumors. Currently, there are very few mouse models of spontaneous lung cancer that are available to validate human lung carcinogenesis. Male C57/BL6 x Balb/c F1 (CB6 F1) mice have a high incidence of pulmonary adenocarcinoma that increases with increasing age. For example, 28 month old males have a 52 per cent incidence, while 32 month old males have close to 80 per cent incidence. In order to determine if these tumors were driven by mitochondrial reactive oxygen species (ROS), we crossed wild type Balb/c females with transgenic males on the C57/BL6 background expressing human catalase targeted to mitochondria (mCAT). The offspring were followed through the end of their lifespan when tissues were collected for histological evaluation. Of 65 males examined, we found that those expressing mCAT had a 29 per cent incidence of lung tumors, while wild type littermates had an incidence of 71 per cent (p ≤ 0.01). The presence of mCAT had a similar effect on the incidence of lung tumors in females although the overall incidence was less than in males. Histologically, lung tumors in wild type mice had higher grade malignancy than lung tumors in mice expressing mCAT suggesting that ROS generated by mitochondria might be playing a role in driving this type of cancer in mice. We conclude that spontaneous lung adenocarcinoma in old CB6 F1 mice could be a useful model to study the anti-tumor effect of mitochondrial-targeted anti-oxidants for intervention of human lung cancer. Citation Format: Christina Pettan-Brewer, John Morton, Piper Treuting, Warren Ladiges. Transgenic C57/BL6 x Balb/c F1 mice expressing mitochondrial targeted catalase have less spontaneous lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 343. doi:10.1158/1538-7445.AM2013-343 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.