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Nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone‐induced pulmonary adenocarcinomas in Syrian golden hamsters contain beta 2‐adrenergic receptor single‐nucleotide polymorphisms
Author(s) -
Masi Thomas,
Cekanova Maria,
Walker Kindra,
Bernert Heike,
Majidi Mourad,
Becker Jeffrey M.,
Schuller Hildegard M.
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20228
Subject(s) - single nucleotide polymorphism , nitrosamine , carcinogen , mesocricetus , cancer research , nonsynonymous substitution , biology , adenocarcinoma , receptor , gene , chemistry , cancer , genetics , endocrinology , genotype , hamster , genome
Cigarette smoking contributes to the development of lung cancer throughout the world, with cases of pulmonary adenocarcinoma (PAC) the most numerous. Nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), which is formed from nicotine, has been demonstrated to cause mutations in genes that affect cell regulation and proliferation. Moreover, NNK has been shown to interact directly with and stimulate beta adrenergic receptor ( ADRB ) signal transduction pathways. Our goal was to determine whether single‐nucleotide polymorphisms (SNPs) in the Adrb2 from PAC tumors were induced in golden hamsters by the injection of NNK. Here we report the cloning and sequencing of Adrb2 clones from either dissected lung tumors from NNK‐injected animals or whole‐lung tissue from water‐injected controls. Both sets of animals contained SNPs; however, we found significantly more SNPs in the Adrb2 from NNK‐injected animals than in the controls. The majority of these SNPs were novel, nonsynonymous mutations found in regions of the Adrb2 known to be involved in ligand binding, G‐protein coupling, and desensitization/down‐regulation. Our data verified the mutagenic effects of NNK as well as demonstrated that this animal model provides an outstanding way of identifying mutations not only in the Adrb2 , but also in other genes that may play essential roles in the regulation and growth of pulmonary adenocarcinomas. © 2005 Wiley‐Liss, Inc.