Archives of Toxicology

, Volume 87, Issue 5, pp 915–918

Oxidative stress in the lung of mice exposed to cigarette smoke either early in life or in adulthood

  • Rosanna T. Micale
  • Sebastiano La Maestra
  • Angela Di Pietro
  • Giuseppa Visalli
  • Barbara Baluce
  • Roumen Balansky
  • Vernon E. Steele
  • Silvio De Flora
Short Communication

Abstract

Birth and early life stages are critical periods characterized by severe alterations of the redox balance and by “physiological” genomic changes in lung cells, which may be responsible for cancer and other diseases in adulthood. Oxidative stress is a major mechanism accounting for the carcinogenicity of cigarette smoke (CS), which becomes more potently carcinogenic in mice when exposure starts at birth and continues early in life. We compared herewith a variety of end-points related to oxidative stress, mitochondrial alterations, and cell turnover in the lung of Swiss H mice, either sham-exposed or CS-exposed for 4 weeks, starting either at birth or at 4 months of age. The results showed that the physiological levels of certain end-points are affected by age. In fact, the baseline proportion of hypodiploid cells and the mitochondrial potential and mass were higher in adults, whereas 8-hydroxy-2′-deoxyguanosine (8-oxo-dGuo) levels, the proportion of necrotic cells, and the extent of autophagy were higher early in life. Adult mice were more responsive to CS by increasing the proportion of necrotic cells and of cells in S/G2 phase, whereas young mice maintained a high extent of autophagy, exhibited a greater increase of lipid peroxidation products and 8-oxo-dGuo levels, and had a higher frequency of micronucleated cells. In addition, exposure to CS affected the mitochondrial potential/mass, especially in young mice. In conclusion, these data provide evidence that oxidative stress and the resulting DNA damage provide a major contribution to the high susceptibility of mice to CS early in life.

Keywords

Cigarette smoke Mouse lung Age Oxidative stress Mitochondrial alterations 

Supplementary material

204_2012_993_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)

References

  1. Balansky R, Ganchev G, Iltcheva M, Steele VE, D’Agostini F, De Flora S (2007) Potent carcinogenicity of cigarette smoke in mice exposed early in life. Carcinogenesis 28:2236–2243PubMedCrossRefGoogle Scholar
  2. Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S (2009) Prenatal N-acetylcysteine prevents cigarette smoke-induced lung cancer in neonatal mice. Carcinogenesis 30:1398–1401PubMedCrossRefGoogle Scholar
  3. Balansky R, Ganchev G, Iltcheva M, Nikolov M, Steele VE, De Flora S (2012a) Differential carcinogenicity of cigarette smoke in mice exposed either transplacentally, early in life or in adulthood. Int J Cancer 130:1001–1010PubMedCrossRefGoogle Scholar
  4. Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S (2012b) Transplacental antioxidants inhibit lung tumors in mice exposed to cigarette smoke after birth: a novel preventative strategy? Curr Cancer Drug Targets 12:164–169PubMedCrossRefGoogle Scholar
  5. Beebe LE, Kim YE, Amin S, Riggs CW, Kovatch RM, Anderson LM (1993) Comparison of transplacental and neonatal initiation of mouse lung and liver tumors by N-nitrosodimethylamine (NDMA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and promotability by a polychlorinated biphenyls mixture (Aroclor 1254). Carcinogenesis 14:1545–1548PubMedCrossRefGoogle Scholar
  6. Buening MK, Wislocki PG, Levin W, Yagi H, Thakker DR, Akagi H, Koreeda M, Jerina DM, Conney AH (1978) Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc Natl Acad Sci USA 75:5358–5361PubMedCrossRefGoogle Scholar
  7. D’Agostini F, Balansky R, Steele VE, Ganchev G, Pesce C, De Flora S (2008) Preneoplastic and neoplastic lesions in the lung, liver and urinary tract of mice exposed to environmental cigarette smoke and UV light since birth. Int J Cancer 123:2497–2502PubMedCrossRefGoogle Scholar
  8. De Flora S, D’Agostini F, Balansky R, Camoirano A, Cartiglia C, Longobardi M, Travaini G, Steele VE, Pesce C, Izzotti A (2008) High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light. Mutat Res Rev 659:137–146CrossRefGoogle Scholar
  9. Droge W (2002) Free radicals in the physiological control of cell function. Physiol 82:47–95Google Scholar
  10. Faux SP, Tai T, Thorne D, Xu Y, Breheny D, Gaca C (2009) The role of oxidative stress in the biological responses of lung epithelial cells to cigarette smoke. Biomarkers 14:90–96PubMedCrossRefGoogle Scholar
  11. Frank L (1985) Effects of oxygen on the newborn. Fed Proc 44:2328–2334PubMedGoogle Scholar
  12. Friel JK, Friesen RW, Harding SV, Roberts LJ (2004) Evidence of oxidative stress in full-term healthy infants. Pediatr Res 56:878–882PubMedCrossRefGoogle Scholar
  13. Fujii K (1991) Evaluation of the newborn mouse model for chemical tumorigenesis. Carcinogenesis 12:1409–1415PubMedCrossRefGoogle Scholar
  14. Gopinathan V, Miller NJ, Milner AD, Rice-Evans CA (1994) Bilirubin and ascorbate antioxidant activity in neonatal plasma. FEBS Lett 349:197–200PubMedCrossRefGoogle Scholar
  15. Izzotti A, Balansky R, Camoirano A, Cartiglia C, Longobardi M, Tampa E, De Flora S (2003) Birth-related genomic and transcriptional changes in mouse lung. Modulation by transplacental N-acetylcysteine. Mutat Res Rev 544:441–449CrossRefGoogle Scholar
  16. Portugal GS, Wilkinson DS, Turner JR, Blendy JA, Gould TJ (2012) Developmental effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning. Neurobiol Learn Mem 97:482–494PubMedCrossRefGoogle Scholar
  17. Wojcik M, Burzynska-Pedziwiatr I, Wozniak LA (2010) A review of natural and synthetic antioxidants important for health and longevity. Curr Med Chem 17:3262–3288PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Rosanna T. Micale
    • 1
  • Sebastiano La Maestra
    • 1
  • Angela Di Pietro
    • 2
  • Giuseppa Visalli
    • 2
  • Barbara Baluce
    • 2
    • 3
  • Roumen Balansky
    • 1
    • 4
  • Vernon E. Steele
    • 5
  • Silvio De Flora
    • 1
  1. 1.Department of Health SciencesUniversity of GenoaGenoaItaly
  2. 2.Department of Hygiene, Public Health and Preventive MedicineUniversity of MessinaMessinaItaly
  3. 3.Cell Factory, Department of Regenerative Medicine, Fondazione IRCCS Ca’ GrandaOspedale Maggiore PoliclinicoMilanItaly
  4. 4.National Center of OncologySofiaBulgaria
  5. 5.National Cancer InstituteRockvilleUSA

Personalised recommendations