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Induction and modulation of lung tumors: genomic and transcriptional alterations in cigarette smoke-exposed mice. Exp Lung Res 2005 Jan-Feb;31(1):19-35

Date

03/16/2005

Pubmed ID

15765917

DOI

10.1080/01902140490494986

Scopus ID

2-s2.0-11144225084   17 Citations

Abstract

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 RM

Author

Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Adenocarcinoma
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
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a