Genetic Influence on Type 2 or Clara Cell Origin of Pulmonary Adenomas in Urethan-Treated Mice23

Abstract

Urethan-induced lung adenomas arising from alveolar type 2 cells and from bronchiolar Clara cells have distinct histologic patterns; and examination of all lung adenomas found in A/J, SWR/J, BALB/cByJ, 129/J, and RIIIS/J inbred mice, 14–16 weeks after a single urethan injection, demonstrated that both tumor types were present in all five strains. The relative numbers of each tumor type varied significantly among the different strains. No correlation was observed between the type of tumor formed and tumor multiplicity. Augmentation of tumor multiplicity by chronic butylated hydroxytoluene (BHT) treatment following urethan injection did not change the proportion of the 2 tumors from that observed with urethan alone. This finding demonstrated that BHT stimulated the development of both tumor types equally. The tumors found 14 weeks after a single urethan injection into neonatal BALB mice were larger than those found 14 weeks after urethan injection into adult BALB mice, but the proportion of alveolar and papillary tumors was the same for both groups. Lymphocytic infiltration into tumors was mainly associated with Clara cell-derived tumors. The proportion of type 2 cell- and Clara cell-derived lung adenomas appeared to be controlled primarily by the genetic background.