Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung.
Post-genomic methodologies have provided novel tools for evaluating safety and efficacy of cancer chemopreventive agents. We exposed rats to environmental cigarette smoke (ECS) for 28 days, with or without oral administration of N-acetylcysteine (NAC). As assessed by 32P-postlabelling, ECS caused a 10-fold increase of DNA adduct levels, which were significantly reduced by NAC. Of 518 proteins tested by antibody microarray, ECS stimulated 56 activities involved in stress response, protein removal, cell replication, apoptosis, phagocytosis, and immune response. NAC alone did not change the amounts of any protein, whereas it significantly decreased the amounts of 6 ECS-induced proteins. The intensity of expression of 278 related genes, assessed by cDNA microarray, was significantly correlated with protein amounts. These observed molecular alterations, which can be attenuated by NAC, represent in part adaptive responses and in part reflect mechanisms contributing to the pathogenesis of smoke-related diseases, including lung cancer, asthma, chronic bronchitis, and emphysema.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy.
Bagnasco
Maria
M
Cartiglia
Cristina
C
Longobardi
Mariagrazia
M
Balansky
Roumen M
RM
Merello
Andrea
A
Lubet
Ronald A
RA
De Flora
Silvio
S
D000818:Animals; D015153:Blotting, Western; D018736:DNA Adducts / Q000187:drug effects; D015870:Gene Expression; D016678:Genome / Q000187:drug effects*; D008175:Lung Neoplasms / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D046228:Microarray Analysis; D020543:Proteome / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000032:analysis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*; D016019:Survival Analysis; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D018736:DNA Adducts; D020543:Proteome; D011663:Pulmonary Surfactants; D014028:Tobacco Smoke Pollution