title: Interactions between ethanol and cigarette smoke in a mouse lung carcinogenesis model.
abstract: Both ethanol and cigarette smoke are classified as human carcinogens. They can synergize, especially in tissues of the upper aerodigestive tract that are targeted by both agents. The main objective of the present study was to evaluate the individual and combined effects of ethanol and smoke in the respiratory tract, either following transplacental exposure and/or postnatal exposure. We designed two consecutive studies in mouse models by exposing Swiss H mice to oral ethanol and/or inhaled mainstream cigarette smoke for up to 4 months, at various prenatal and postnatal life stages. Clastogenic effects and histopathological alterations were evaluated after 4 and 8 months, respectively. Ethanol was per se devoid of clastogenic effects in mouse peripheral blood erythrocytes. However, especially in mice exposed both transplacentally throughout pregnancy and in the postnatal life, ethanol administration was associated not only with liver damage but also with pro-angiogenetic effects in the lung by stimulating the proliferation of blood vessels. In addition, these mice developed pulmonary emphysema, alveolar epithelial hyperplasias, microadenomas, and benign tumors. On the other hand, ethanol interfered in the lung carcinogenesis process resulting from the concomitant exposure of mice to smoke. In fact, ethanol significantly attenuated some smoke-related preneoplastic and neoplastic lesions in the respiratory tract, such as alveolar epithelial hyperplasia, microadenomas, and even malignant tumors. In addition, ethanol attenuated cigarette smoke clastogenicity. In conclusion, preclinical studies provide evidence that, in spite of its pulmonary toxicity, ethanol may mitigate some noxious effects of cigarette smoke in the respiratory tract.
authors.affiliation: National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rubalansky@sbaloncology.bg.
authors.forename: Roumen
authors.initials: R
authors.lastname: Balansky
authors.affiliation: National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: drganchoganchev@abv.bg.
authors.forename: Gancho
authors.initials: G
authors.lastname: Ganchev
authors.affiliation: National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mariettailtcheva@yahoo.com.
authors.forename: Marietta
authors.initials: M
authors.lastname: Iltcheva
authors.affiliation: National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mdn@mail.bg.
authors.forename: Manasi
authors.initials: M
authors.lastname: Nikolov
authors.affiliation: Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: lamaestra78@yahoo.it.
authors.forename: S
authors.initials: S
authors.lastname: La Maestra
authors.affiliation: Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rosannamicale@yahoo.it.
authors.forename: Rosanna T
authors.initials: RT
authors.lastname: Micale
authors.affiliation: National Cancer Institute, Chemoprevention Agent Development Research Group, Division of Cancer Prevention,9609 Medical Center Drive, Bethesda, MD 20892, USA. Electronic address: steelev@mail.nih.gov.
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Steele
authors.affiliation: Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: sdf@unige.it.
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D012906:Smoke / Q000009:adverse effects*; D016019:Survival Analysis; D014026:Nicotiana; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D002492:Central Nervous System Depressants; D009153:Mutagens; D012906:Smoke; D014028:Tobacco Smoke Pollution; D000431:Ethanol
keywords: Cigarette smoke; Cytogenetic damage; Ethanol; Histopathological alterations; Lung tumors