title: Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the modulating effect of hyperoxia.
abstract: 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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
authors.forename: H M
authors.initials: HM
authors.lastname: Schuller
authors.forename: H P
authors.initials: HP
authors.lastname: Witschi
authors.forename: E
authors.initials: E
authors.lastname: Nylen
authors.forename: P A
authors.initials: PA
authors.lastname: Joshi
authors.forename: E
authors.initials: E
authors.lastname: Correa
authors.forename: K L
authors.initials: KL
authors.lastname: Becker
mesh_terms: 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*
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D001839:Bombesin; D010100:Oxygen