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Mutations of the Smad2 and Smad4 genes in lung adenocarcinomas induced by N ‐nitrosobis(2‐hydroxypropyl)amine in rats
Author(s) -
Tsujiuchi Toshifumi,
Sasaki Yasutaka,
Tsutsumi Masahiro,
Konishi Yoichi
Publication year - 2000
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/1098-2744(200010)29:2<87::aid-mc5>3.0.co;2-r
Subject(s) - biology , adenocarcinoma , transition (genetics) , gene , microbiology and biotechnology , mutation , lung , rna , cancer research , genetics , medicine , cancer
Mutations of the Smad2 and Smad4 genes, identified as mediators of the transforming growth factor‐β 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. Mol. Carcinog. 29:87–91, 2000. © 2000 Wiley‐Liss, Inc.