Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the modulating effect of hyperoxia.
Neuroendocrine lung cancer is among the most common types of lung cancers in smokers. We have recently shown that exposure of hamsters to N-nitrosodiethylamine and hyperoxia causes a high incidence of this tumor type. In this study, we show that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone also causes neuroendocrine lung tumors in hyperoxic hamsters. Animals maintained in ambient air while being treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone developed pulmonary adenomas composed of Clara cells and alveolar type II cells. Pathogenesis experiments provide evidence for the tumors caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in ambient air being derived from Clara cells. In the hyperoxic hamsters, the neuroendocrine carcinogenesis appears to involve two stages: (a) transformation of focal alveolar type II cells into neuroendocrine cells and (b) development of neuroendocrine lung tumors from such foci.
Schuller
H M
HM
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Witschi
H P
HP
Nylen
E
E
Joshi
P A
PA
Correa
E
E
Becker
K L
KL
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology* / Q000648:ultrastructure; D000388:Air; D000818:Animals; D001839:Bombesin / Q000032:analysis; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D008854:Microscopy, Electron; D009490:Neurosecretory Systems / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009602:Nitrosamines / Q000633:toxicity*; D010100:Oxygen / Q000494:pharmacology*
D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D001839:Bombesin; D010100:Oxygen