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Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and cigarette smoke in mouse liver and lung
Alberto Izzotti1, Patrizia Larghero, Cristina Cartiglia
1Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy.
Abstract:
Although microRNAs (miRNA) have extensively been investigated in cancer research, less attention has been paid to their regulation by carcinogens and/or protective factors in early stages of the carcinogenesis process. The present study was designed to evaluate the modulation of mRNA expression as related to exposure of neonatal mice to environmental cigarette smoke (ECS) and to treatment with chemopreventive agents. Exposure to ECS started immediately after birth and for 2 weeks after weaning. Thereafter, groups of mice received daily either budesonide (BUD) or phenethyl isothiocyanate (PEITC) with the diet. The expression of 576 miRNAs was evaluated by miRNA microarray in liver and lung. In sham-exposed mice, the expression of miRNAs tended to be higher in liver than in lung. ECS downregulated the expression of a number of miRNAs in lung, whereas mixed alterations were observed in liver. PEITC and BUD did not substantially affect the physiological situation in lung, whereas both agents caused intense variations in liver, reflecting the occurrence of damage mechanisms, such as inflammation, DNA and protein damage, cellular stress, proliferation and apoptosis. PEITC and BUD protected the lung from ECS-induced alterations of miRNA expression but exhibited some adverse effects in liver.
Insights
Environmental cigarette smoke (ECS) alters microRNA (miRNA) expression in neonatal mice lungs and livers. Chemopreventive agents budesonide and phenethyl isothiocyanate protected lungs but caused liver damage.
Area of Science:
- Environmental toxicology
- Molecular biology
- Carcinogenesis research
Background:
- MicroRNAs (miRNAs) are crucial in cancer, but their regulation by carcinogens in early carcinogenesis is understudied.
- Environmental cigarette smoke (ECS) is a known carcinogen, yet its impact on miRNA expression during early development requires further investigation.
- Chemopreventive agents offer potential protection against carcinogen-induced damage.
Purpose of the Study:
- To investigate the effects of ECS exposure on miRNA expression in neonatal mice.
- To evaluate the modulatory effects of budesonide (BUD) and phenethyl isothiocyanate (PEITC) on miRNA expression following ECS exposure.
- To assess the protective or detrimental impacts of BUD and PEITC on lung and liver tissues.
Main Methods:
- Neonatal mice were exposed to ECS.
- Post-weaning, mice received daily doses of BUD or PEITC.
- miRNA expression profiling of 576 miRNAs was performed on liver and lung tissues using microarray analysis.
Main Results:
- ECS exposure downregulated several miRNAs in the lung and caused mixed alterations in the liver.
- BUD and PEITC treatments did not significantly alter lung miRNA expression but induced substantial changes in the liver, indicating damage mechanisms like inflammation and apoptosis.
- BUD and PEITC demonstrated a protective effect on lung miRNA expression against ECS-induced changes.
Conclusions:
- ECS significantly impacts miRNA expression in neonatal mouse lungs and livers.
- Chemopreventive agents BUD and PEITC protect the lung from ECS-induced miRNA dysregulation.
- BUD and PEITC exhibit adverse effects on the liver, suggesting tissue-specific responses to these agents.
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