Carcinogenesis Advance Access originally published online on May 23, 2007
Carcinogenesis 2007 28(10):2236-2243; doi:10.1093/carcin/bgm122
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Potent carcinogenicity of cigarette smoke in mice exposed early in life
1 Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy
2 National Center of Oncology, Sofia 1756, Bulgaria
3 National Cancer Institute, Rockville, MD 20892, USA
* To whom correspondence should be addressed. Tel: +39 010 3538500; Fax: +39 010 3538504; Email: sdf{at}unige.it.
In spite of the dominant role of cigarette smoke (CS) in cancer epidemiology, all studies performed during the past 60 years have shown that this complex mixture is either negative or weakly tumorigenic in experimental animals. We implemented studies aimed at evaluating whether exposure of mice early in life may enhance susceptibility to CS carcinogenicity. A total of 98 newborn Swiss albino mice were either untreated (controls) or received a subcutaneous injection of benzo(a)pyrene [B(a)P] (positive control) or were exposed whole-body to mainstream cigarette smoke (MCS) for 120 days, starting within 12 h after birth. Complete necropsy and histopathological analyses were performed at periodical intervals. In contrast with the lack of lung tumors in controls, MCS-exposed mice developed microscopically detectable tumors, starting only 75 days after birth and reaching an overall incidence of 78.3% after 181–230 days. The mean lung tumor multiplicities were 6.1 and 13.6 tumors per mouse in males and females, respectively, showing a significant intergender difference. Most tumors were microadenomas or adenomas, but 18.4% of the mice additionally had malignant lung cancer. MCS also induced bronchial and alveolar epithelial hyperplasia, and blood vessel proliferation. Furthermore, malignant tumors, some of which may have a metastatic origin, were detected in the urinary tract and liver of MCS-exposed mice. A somewhat different spectrum of tumors was observed in B(a)P-treated mice. In conclusion, MCS is a potent and broad spectrum carcinogen in mice when exposure starts early in life, covering stages of life corresponding to neonatal, childhood and adolescence periods in humans. This animal model will be useful to explore the mechanisms involved in CS-induced carcinogenesis and to investigate the protective effects of dietary agents and chemopreventive drugs.
Abbreviations: B(a)P, benzo(a)pyrene; CS, cigarette smoke; ECS, environmental cigarette smoke; MCS, mainstream cigarette smoke
Received March 19, 2007; revised May 9, 2007; accepted May 10, 2007.
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