title: Potent carcinogenicity of cigarette smoke in mice exposed early in life.
abstract: 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.
authors.affiliation: Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy.
authors.forename: Roumen
authors.initials: R
authors.lastname: Balansky
authors.forename: Gancho
authors.initials: G
authors.lastname: Ganchev
authors.forename: Marietta
authors.initials: M
authors.lastname: Iltcheva
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Steele
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Agostini
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004781:Environmental Exposure; D005260:Female; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000209:etiology / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015430:Weight Gain
chemical_list: D002273:Carcinogens; D014028:Tobacco Smoke Pollution; D001564:Benzo(a)pyrene