microRNA expression in rat lung receiving chemopreventive agents and attenuation of cigarette smoke-induced alterations

We previously showed that exposure of rats to environmental cigarette smoke (ECS) causes extensive downregulation of microRNA expression in the lung, resulting in overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lung of rats receiving orally chemopreventive agents, including N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone and phenethyl isothiocyanate, or combinations thereof. Scatterplot, hierarchical cluster, and principal component analyses showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, while all of them attenuated ECS-induced alterations but to a variable extent. Thus, mirnome analysis provides a new tool for predicting both safety and efficacy of cancer chemopreventive agents at early carcinogenesis stages. Keywords: cancer chemoprevention, microRNA, environmental cigarete smoke (ECS), 5,6-benzoflavone (BF), Indole 3-carbinol (I3C),N-acetylcysteine (NAC), oltipraz (OPZ), Phenethyl isothiocyanate (PEITC). Adult male Sprague-Dawley rats (Harlan Italy, Correzzana, Milan, Italy), weighing 315-320 g, were divided into 16 groups, each composed of 8 animals. Half of them were exposed to ECS for 28 consecutive days, as previously described (Izzotti et al., 2005), while the remaining rats (Sham-exposed) were kept for the same period of time in filtered air. The rats belonging to 14 groups were treated with chemopreventive agents, starting 3 days before exposure to ECS.