Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung
| Autor: | Mariagrazia Longobardi, Silvio De Flora, Alberto Izzotti, Anna Camoirano, Vernon E. Steele, Patrizia Larghero, Cristina Cartiglia |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Microarray Health Toxicology and Mutagenesis medicine.disease_cause DNA Adducts Mice Downregulation and upregulation Pregnancy Smoke Internal medicine Tobacco microRNA Sense (molecular biology) Genetics medicine Animals Cluster Analysis Lung Molecular Biology Principal Component Analysis Dose-Response Relationship Drug Microarray analysis techniques business.industry Smoking Deoxyguanosine Microarray Analysis Rats MicroRNAs Dose–response relationship Endocrinology medicine.anatomical_structure Animals Newborn Gene Expression Regulation 8-Hydroxy-2'-Deoxyguanosine Female Smoking Cessation Tobacco Smoke Pollution business Carcinogenesis Biomarkers |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 717:9-16 |
| ISSN: | 0027-5107 |
| DOI: | 10.1016/j.mrfmmm.2010.12.008 |
| Popis: | Our previous studies demonstrated that exposure to cigarette smoke (CS), either mainstream or environmental, results in a remarkable downregulation of microRNA expression in the lung of both mice and rats. The goals of the present study were to evaluate the dose responsiveness to CS and the persistence of microRNA alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole-body to mainstream CS, at the doses of 119, 292, 438, and 631mg/m(3) of total particulate matter. Exposure started within 12h after birth and continued daily for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were measured by (32)P postlabeling procedures, and the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS dose was lethal. Exposure to CS caused a dose-dependent increase of DNA alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4 weeks after smoking cessation. Exposure to CS resulted in an evident dysregulation of microRNA expression profiles, mainly in the sense of downregulation. The two lowest doses were not particularly effective, while the highest nonlethal dose produced extensive microRNA alterations. The expression of most downregulated microRNAs, including among others 7 members of the let-7 family, was restored one week after smoking cessation. However, the recovery was incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421, mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as biomarkers of effect and that exposure to high-dose, lasting for an adequate period of time, is needed to trigger the CS-related carcinogenesis process in the experimental animal model used. |
| Databáze: | OpenAIRE |
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