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.
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Acknowledgments
The authors acknowledge the financial support by the US National Cancer Institute (contract N01-CN53301), the Bulgarian Ministry of Youth and Science (National Science Fund), and the Hasumi International Foundation. The authors thank Dr. Ilaria Righi for her contribution in preparing the manuscript.
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Micale, R.T., Maestra, S.L., Pietro, A.D. et al. Oxidative stress in the lung of mice exposed to cigarette smoke either early in life or in adulthood. Arch Toxicol 87, 915–918 (2013). https://doi.org/10.1007/s00204-012-0993-1
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DOI: https://doi.org/10.1007/s00204-012-0993-1