Elevated expression of transforming growth factor betas and the tumor necrosis factor family in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.
Expression of transforming growth factor betas (TGF betas), tumor necrosis factor (TNF) family members, interferons (IFNs), macrophage migration inhibitory factor (MIF) and granulocyte macrophage colony stimulating factor (GM-CSF) in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats was investigated using a multiprobe RNase protection assay (RPA) followed by densitometric quantification. Male Wistar rats, 6 weeks of age, were given 2,000 ppm BHP in their drinking water for 12 weeks and maintained without further treatment until killed at week 25. Total RNAs were extracted from 15 adenocarcinomas. Four samples of normal lung tissue from untreated rats served as controls. The expression of TGFbeta1, TGFbeta2, TGFbeta3, TNFalpha, TNFbeta and lymphotoxin beta (Ltbeta) 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 IFNbeta, IFNgamma and GM-CSF was apparent in either adenocarcinomas or normal lung tissues. These results suggest that elevated expression of TGFbetas and TNF family members may contribute to the development and progression of lung adenocarcinomas induced by BHP in rats.
Tsujiuchi
T
T
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan. ttujiuch@nmu-gw.naramed-u.ac.jp
Sasaki
Y
Y
Murata
N
N
Tsutsumi
M
M
Nakae
D
D
Konishi
Y
Y
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004326:Drinking; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009602:Nitrosamines / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D002273:Carcinogens; D009602:Nitrosamines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C012457:diisopropanolnitrosamine