High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light

Silvio De Flora, Francesco D'Agostini, Roumen Balansky, Anna Camoirano, Cristina Cartiglia, Mariagrazia Longobardi, Giorgia Travaini, Vernon E. Steele, Carlo Pesce, Alberto Izzotti

Research output: Contribution to journalArticle

Abstract

Our recent studies have shown that both cigarette smoke and UV-containing light, which are the most widespread and ubiquitous mutagens and carcinogens in the world, cause systemic genotoxic damage in hairless mice. Further studies were designed with the aim of evaluating the induction of genotoxic and carcinogenic effects in Swiss albino mice exposed to smoke and/or light since birth. We observed that a 4-month whole-body exposure of mice to mainstream cigarette smoke, starting at birth, caused an early and potent carcinogenic response in the lung and other organs. Our further experiments showed that exposure of mice to environmental cigarette smoke, during the first 5 weeks of life, resulted in a variety of significant alterations of intermediate biomarkers, including cytogenetic damage in bone marrow and peripheral blood, formation of lipid peroxidation products, increase of bulky DNA adduct levels, induction of oxidative DNA damage, and overexpression of OGG1 gene in lung, stimulation of apoptosis, hyperproliferation and loss of Fhit protein in pulmonary alveolar macrophages and/or bronchial epithelial cells, and early histopathological alterations in the respiratory tract. Moreover, exposure of mice to UV-containing light, mimicking solar irradiation, significantly enhanced oxidative DNA damage and bulky DNA adduct levels in lung, and synergized with smoke in inducing molecular alterations in the respiratory tract. The baseline OGG1 expression in lung was particularly high at birth and decreased in post-weanling mice. Oxidative DNA damage and other investigated end-points exhibited differential patterns in post-weanling mice and adult mice. The findings of these studies provide a mechanistic clue to the general concept that the neonatal period and early stages of life are critical in affecting susceptibility to carcinogens.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalMutation Research - Reviews in Mutation Research
Volume659
Issue number1-2
DOIs
Publication statusPublished - Jul 2008

Keywords

  • Carcinogenicity
  • Environmental cigarette smoke
  • Genotoxicity
  • Intermediate biomarkers
  • Mainstream cigarette smoke
  • Neonatal mice
  • UV-containing light

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis

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