title: Mutations of the Smad2 and Smad4 genes in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.
abstract: Mutations of the Smad2 and Smad4 genes, identified as mediators of the transforming growth factor-beta pathway, were investigated in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 wk old, were given 2000 ppm BHP in their drinking water for 12 wk and maintained without additional treatment until killed at week 25. Total RNA was extracted from 12 adenocarcinomas, and mutations in Smad2 and Smad4 were investigated by reverse transcription-polymerase chain reaction restriction single-strand conformation polymorphism analysis followed by sequencing analysis. In Smad2, single adenocarcinomas showed a GGC to GAC (Gly to Asp) transition at codon 100 and an AAG to GAG (Lys to Glu) transition at codon 383. In Smad4, one adenocarcinoma exhibited a TTC to CTC (Phe to Leu) transition at codon 214. These results suggest that mutations of Smad2 and Smad4 may play roles in a limited fraction of lung adenocarcinomas induced by BHP in rats.
authors.affiliation: Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D002273:Carcinogens; D004268:DNA-Binding Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D009154:Mutation; D009602:Nitrosamines; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D002273:Carcinogens; D004268:DNA-Binding Proteins; D009602:Nitrosamines; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D015534:Trans-Activators; C012457:diisopropanolnitrosamine