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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.

SUBMITTER: Gordon W

PROVIDER: S-EPMC3587785 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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The tobacco carcinogen nitrosamine induces a differential gene expression response in tumour susceptible A/J and resistant C3H mouse lungs.

Gordon William W Galitovskiy Valentin V Edwards Robert R Andersen Bogi B Grando Sergei A SA

European journal of cancer (Oxford, England : 1990) 20120923 3

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 ...[more]

PMID: 23010150

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Project description:Rosellinia necatrix is the causal agent of avocado white root rot (WRR). Control of this soil-borne disease is difficult, and the use of tolerant rootstocks may present an effective method to lessen its impact. To date, no studies on the molecular mechanisms regulating the avocado plant response towards this pathogen have been undertaken. To shed light on the mechanisms underpinning disease susceptibility and tolerance, molecular analysis of the gene's response in two avocado rootstocks with a contrasting disease reaction was assessed. Gene expression profiles against R. necatrix were carried out in the susceptible 'Dusa' and the tolerant selection BG83 avocado genotypes by micro-array analysis. In 'Dusa', the early response was mainly related to redox processes and cell-wall degradation activities, all becoming enhanced after disease progression affected photosynthetic capacity, whereas tolerance to R. necatrix in BG83 relied on the induction of protease inhibitors and their negative regulators, as well as genes related to tolerance to salt and osmotic stress such as aspartic peptidase domain-containing proteins and gdsl esterase lipase proteins. In addition, three protease inhibitors were identified, glu protease, trypsin and endopeptidase inhibitors, which were highly overexpressed in the tolerant genotype when compared to susceptible 'Dusa', after infection with R. necatrix, reaching fold change values of 52, 19 and 38, respectively. The contrasting results between 'Dusa' and BG83 provide new insights into the different mechanisms involved in avocado tolerance to Phytophthora cinnamomi and R. necatrix, which are consistent with their biotrophic and necrotrophic lifestyles, respectively. The differential induction of genes involved in salt and osmotic stress in BG83 could indicate that R. necatrix penetration into the roots is associated with osmotic effects, suggesting that BG83's tolerance to R. necatrix is related to the ability to withstand osmotic imbalance. In addition, the high expression of protease inhibitors in tolerant BG83 compared to susceptible 'Dusa' after infection with the pathogen suggests the important role that these proteins may play in the defence of avocado rootstocks against R. necatrix.

Dataset Information

The tobacco carcinogen nitrosamine induces a differential gene expression response in tumour susceptible A/J and resistant C3H mouse lungs.

Publications

The tobacco carcinogen nitrosamine induces a differential gene expression response in tumour susceptible A/J and resistant C3H mouse lungs.

Similar Datasets

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