title: Oxidative stress in the lung of mice exposed to cigarette smoke either early in life or in adulthood.
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.
authors: Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132, Genoa, Italy. rosannamicale@yahoo.it
authors: Rosanna T
authors: RT
authors: Micale
authors: Sebastiano
authors: S
authors: La Maestra
authors: Sebastiano La
authors: SL
authors: Maestra
authors: Angela
authors: A
authors: Di Pietro
authors: Angela Di
authors: AD
authors: Pietro
authors: Giuseppa
authors: G
authors: Visalli
authors: Barbara
authors: B
authors: Baluce
authors: Roumen
authors: R
authors: Balansky
authors: Vernon E
authors: VE
authors: Steele
authors: Silvio
authors: S
authors: De Flora
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000782:Aneuploidy; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D019570:Inhalation Exposure; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D012906:Smoke; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine