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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 296/3/L418    most recent 90382.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cavarra, E. Articles by Varesio, L. Search for Related Content PubMed PubMed Citation Articles by Cavarra, E. Articles by Varesio, L.

Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke

¹Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Siena; ²Laboratorio di Biologia Molecolare, Istituto G. Gaslini Genova, Genova; ³Clinica di Malattie dell'Apparato Respiratorio, Fondazione IRCCS Policlinico S. Matteo, Università di Pavia, Pavia; and ⁴Istituto Nazionale per la Ricerca sul Cancro di Genova, S. S. Genomica Funzionale, Genova, Italy

Submitted 15 July 2008 ; accepted in final form 24 December 2008

We have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57BL/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, whereas ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype. The three strains of mice were exposed to smoke from three cigarettes per day, 5 days/wk, for 4 wk. Microarray analysis was carried out on total RNA extracted from the lung using the Affymetrix platform. Cigarette smoke modulates several clusters of genes (i.e., proemphysematous, acute phase response, and cell adhesion) in smoke-sensitive DBA/2 or C57BL/6J strains, but the same genes are not altered by smoke in ICR resistant mice. Only a few genes were commonly modulated by smoke in the three strains of mice. This pattern of gene expression suggests that the response to smoke is strain-dependent and may involve different molecular signaling pathways. Real-time quantitative PCR was used to verify the pattern of modulation of selected genes and their potential biological relevance. We conclude that gene expression response to smoke is highly dependent on the mouse genetic background. We speculate that the definition of gene clusters associated, to various degrees, with mouse susceptibility or resistance to smoke may be instrumental in defining the molecular basis of the individual response to smoke-induced lung injury in humans.

emphysema; antioxidant defenses; cigarette smoke susceptibility; mouse strains; microarrays