Cellular derivation of lung tumors in sensitive and resistant strains of mice: results at 28 and 56 weeks after urethan treatment

Abstract

Urethan (CAS: 51-79-6)-induced pulmonary adenomas that arise from either alveolar type II pneumocytes of bronchiolar Clara cells have distinct histologic growth patterns and can thus be distinguished from each other. Strain differences were reported in the relative proportions of tumors derived from each cell type when these tumors were examined 14 weeks after urethan treatment. For determination as to whether these proportions changed at later stages of growth, tumors in A/J, SWR/J, RIIIS/J, BALB/cByJ, 129/J, and C57BL/6J mice were examined at 28 and 56 weeks after urethan treatment. Tumor multiplicity increased with time in all strains. Small tumors were predominantly type II cell derived in most strains, whereas medium and large tumors were derived mainly from Clara cells. This suggests that type II tumors are restricted in growth while Clara tumors may continue to grow. Medium and large Clara-derived tumors made up a larger proportion of the total tumor population at 28 and 56 weeks than at 14 weeks post urethan, even in A/J mice that typically display 85% type II cell-derived tumors at the earlier time. Several large Clara cell-derived tumors exhibited characteristics of cancer, whereas no type II cell-derived tumor was observed to do so. These results implicate the bronchiolar Clara cell as the predominant cell of origin of pulmonary adenocarcinomas in mice.