Tobacco smoking is associated with a variety of chronic degenerative diseases, including cerebrovascular diseases. However, little is known regarding the influence of smoking on neurodegenerative conditions. Studies in rats showed that exposure to cigarette smoke (CS) causes oxidative stress and DNA damage in brain. The goal of the present study was to evaluate the patterns of DNA damage in neonatal mice exposed whole-body to mainstream CS generated in a smoking machine. The litters of 4 pregnant ICR (CD-1) mice, each including an average of 13 neonatal mice, were either kept in filtered air (sham) or exposed to CS at 3 dose levels, corresponding to 150, 310, and 450 mg/m3 of total particulate matter. After 4 weeks the mice were sacrificed, and DNA damage was evaluated by analyzing 400 brain cells/mouse in the single cell gel electrophoresis (SCGE, Comet assay). In neutral environment CS induced a dose-dependent increase of double-strand breaks, with a maximum 2.8-fold variation over sham. Similarly, in alkaline environment CS caused an increase of single-strand breaks, which was statistically significant and dose-dependent, with a maximum 1.6-fold variation over sham. DNA damage was more pronounced in the presence of proteinase K, which is consistent with a major role for DNAprotein crosslinks. In parallel, there was an increase of TBARS (thiobarbituric acid reactive substances), which was statistically significant at the highest CS dose tested. No signs of apoptosis were detectable by TUNEL method. These data show for the first time that exposure to CS produces a significant increase of lipid peroxidation products and DNA damage in the brain of mice exposed early in life. Especially taking into account the poor ability of brain cells to repair DNA damage, these findings may bear relevance in the pathogenesis of smoke-related neurodegenerative diseases.

DNA Damage in the brain of mice exposed to cigarette smoke

LA MAESTRA, SEBASTIANO;MICALE, ROSANNA TINDARA;D'AGOSTINI, FRANCESCO;DE FLORA, SILVIO
2009

Abstract

Tobacco smoking is associated with a variety of chronic degenerative diseases, including cerebrovascular diseases. However, little is known regarding the influence of smoking on neurodegenerative conditions. Studies in rats showed that exposure to cigarette smoke (CS) causes oxidative stress and DNA damage in brain. The goal of the present study was to evaluate the patterns of DNA damage in neonatal mice exposed whole-body to mainstream CS generated in a smoking machine. The litters of 4 pregnant ICR (CD-1) mice, each including an average of 13 neonatal mice, were either kept in filtered air (sham) or exposed to CS at 3 dose levels, corresponding to 150, 310, and 450 mg/m3 of total particulate matter. After 4 weeks the mice were sacrificed, and DNA damage was evaluated by analyzing 400 brain cells/mouse in the single cell gel electrophoresis (SCGE, Comet assay). In neutral environment CS induced a dose-dependent increase of double-strand breaks, with a maximum 2.8-fold variation over sham. Similarly, in alkaline environment CS caused an increase of single-strand breaks, which was statistically significant and dose-dependent, with a maximum 1.6-fold variation over sham. DNA damage was more pronounced in the presence of proteinase K, which is consistent with a major role for DNAprotein crosslinks. In parallel, there was an increase of TBARS (thiobarbituric acid reactive substances), which was statistically significant at the highest CS dose tested. No signs of apoptosis were detectable by TUNEL method. These data show for the first time that exposure to CS produces a significant increase of lipid peroxidation products and DNA damage in the brain of mice exposed early in life. Especially taking into account the poor ability of brain cells to repair DNA damage, these findings may bear relevance in the pathogenesis of smoke-related neurodegenerative diseases.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/870291
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