title: The tobacco carcinogen nitrosamine induces a differential gene expression response in tumour susceptible A/J and resistant C3H mouse lungs.
abstract: The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), an important carcinogen found in tobacco products, causes lung cancer in genetically susceptible animals. In addition to mutations of the K-Ras gene, NNK has non-mutagenic effects that include alterations in gene expression and immunomodulation in the lung. Here we report the identification of two gene sets associated with NNK-induced pulmonary tumourigenesis. First, to identify genes involved in the susceptibility to NNK, we compared the lung transcriptomes of NNK-resistant C3H mice with that of the NNK-susceptible A/J mice, identifying differential expression of genes related to innate immunity and inflammation. Second, to identify gene expression induced by NNK, we compared the lung transcriptomes of C3H and A/J mice post-treatment. The Resistin-like alpha (Retnla) gene was highly upregulated in response to NNK only in susceptible mice. This gene product is known to recruit immune cells to the lung, and accumulation of CD45 positive cells in A/J lungs correlated with increased Retnla expression. Genetic susceptibility to NNK-induced lung tumourigenesis may relate in part to gene expression changes and alterations in the immune response to create a pro-tumourigenic environment, acting in concert with NNK's mutagenic effects.
authors.affiliation: Department of Biological Chemistry, University of California Irvine, Irvine, CA, United States.
authors.forename: William
authors.initials: W
authors.lastname: Gordon
authors.forename: Valentin
authors.initials: V
authors.lastname: Galitovskiy
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grando
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009602:Nitrosamines / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone