Induction and modulation of lung tumors: genomic and transcriptional alterations in cigarette smoke-exposed mice. Exp Lung Res 2005;31(1):19-35
Date
03/16/2005Pubmed ID
15765917DOI
10.1080/01902140490494986Scopus ID
2-s2.0-11144225084 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Cigarette smoke plays a major role in the epidemiology of lung cancer, and smoke components have extensively been investigated in carcinogenicity and chemoprevention studies in experimental animals. However, it is much more difficult to reproduce the tumorigenicity of the whole complex mixture in preclinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transciptional alterations in smoke-exposed mice. The authors were successful in inducing lung tumors in 4 strains of mice exposed whole-body to environmental cigarette smoke, including Swiss albino, A/J, SKH-1 hairless, and p53 mutant (UL533 x A/J)F1 mice. However, the tumorigenic response was rather weak in all strains. Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2-deoxyguanosine; multigene expression, and thiobarbituric acid-reactive aldehydes in whole lung and several other organs. Smoke-induced genomic and transcriptional alterations were suitable for evaluating their modulation by chemopreventive agent, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.
Author List
De Flora S, Izzotti A, D'Agostini F, Bennicelli C, You M, Lubet RA, Balansky RMMESH terms used to index this publication - Major topics in bold
AcetylcysteineAdenocarcinoma
Animals
Anti-Inflammatory Agents, Non-Steroidal
Biomarkers
Carcinogens
Chemoprevention
Disease Models, Animal
Drug Antagonism
Gene Expression Profiling
Inhalation Exposure
Lung Neoplasms
Macrophages, Alveolar
Mice
Mice, Nude
Micronuclei, Chromosome-Defective
Micronucleus Tests
Species Specificity
Sulindac
Tobacco Smoke Pollution
Transcription, Genetic
