Elevated expression of transforming growth factor beta s and the tumor necrosis factor family in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats

Expression of transforming growth factor Ps (TGF Ps), tumor necrosis factor (TNF) family members, interferons (IFNs), macrophage migration inhibitory factor (NEF) and granulocyte macrophage colony stimulating factor (GMCSF) i n lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats was investigated using a multiprobe RNase protection assay (RPA) fo llowed by densitometric quantification. Male Wistar rats, 6 weeks of age, w ere given 2000 ppm BHP in their drinking water for 12 weeks and maintained without further treatment until killed at week 25. Total RNAs were extracte d from 15 adenocarcinomas. Four samples of normal lung tissue from untreate d rats served as controls. The expression of TGF beta1, TGF beta2, TGF beta 3, TNF alpha, TNF beta and lymphotoxin P (Ltp) was significantly higher in adenocarcinomas than in normal lung tissues. In contrast, MIF was expressed at the same level in neoplasms and normal tissue and no expression of IFN beta, IFN gamma and GM-CSF was apparent in either adenocarcinomas or normal lung tissues. These results suggest that elevated expression of TGF betas and TNF family members may contribute to the development and progression of lung adenocarcinomas induced by BHP in rats.