TY - JOUR
T1 - Induction and modulation of lung tumors
T2 - Genomic and transcriptional alterations in cigarette smoke-exposed mice
AU - De Flora, Silvio
AU - Izzotti, Alberto
AU - D'Agostini, Francesco
AU - Bennicelli, Carlo
AU - You, Ming
AU - Lubet, Ronald A.
AU - Balansky, Roumen M.
N1 - Funding Information:
Received 28 November 2003; accepted 19 February 2004. The reported studies were supported by grants from the U.S. National Cancer Institute (Master Agreements N01-CN-75008 and N01-CN-05122), the Associazione Italiana per la Ricerca sul Cancro (AIRC), and the Bulgarian Ministry of Science and Education. Address correspondence to Silvio De Flora, Department of Health Sciences, University of Genoa, Via Pastore 1, I-16132 Genoa, Italy. E-mail: sdf@unige.it
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/1
Y1 - 2005/1
N2 - 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 tumongenicity of the whole complex mixture in pre-clinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transcriptional 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 (UL53-3 × 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 agents, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.
AB - 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 tumongenicity of the whole complex mixture in pre-clinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transcriptional 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 (UL53-3 × 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 agents, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.
KW - Chemoprevention
KW - Cigarette smoke
KW - Genomic alterations
KW - Lung tumors
KW - Murine models
KW - Transcriptional alterations
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U2 - 10.1080/01902140490494986
DO - 10.1080/01902140490494986
M3 - Article
C2 - 15765917
AN - SCOPUS:11144225084
VL - 31
SP - 19
EP - 35
JO - Experimental Lung Research
JF - Experimental Lung Research
SN - 0190-2148
IS - 1
ER -