Open AccessAbstracts from the 8th International Comet Assay Workshop held at the University of Perugia, Perugia, Italy; 27-30 August 2009
Author(s) -
La Maestra, S.,
Micale, R.T.,
Larghero, P.,
D’Agostini, F.,
De Flora, S.
Publication year - 2010
Publication title -
mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.723
H-Index - 91
eISSN - 1464-3804
pISSN - 0267-8357
DOI - 10.1093/mutage/gep062
Subject(s) - library science , computer science
Tobacco smoking is associated with a variety of chronic\uddegenerative diseases, including cerebrovascular diseases.\udHowever, little is known regarding the influence of smoking\udon neurodegenerative conditions. Studies in rats showed that\udexposure to cigarette smoke (CS) causes oxidative stress and\udDNA damage in brain. The goal of the present study was to\udevaluate the patterns of DNA damage in neonatal mice exposed\udwhole-body to mainstream CS generated in a smoking\udmachine. The litters of 4 pregnant ICR (CD-1) mice, each\udincluding an average of 13 neonatal mice, were either kept in\udfiltered air (sham) or exposed to CS at 3 dose levels,\udcorresponding to 150, 310, and 450 mg/m3 of total particulate\udmatter. After 4 weeks the mice were sacrificed, and DNA\uddamage was evaluated by analyzing 400 brain cells/mouse in\udthe single cell gel electrophoresis (SCGE, Comet assay). In\udneutral environment CS induced a dose-dependent increase of\uddouble-strand breaks, with a maximum 2.8-fold variation over\udsham. Similarly, in alkaline environment CS caused an increase\udof single-strand breaks, which was statistically significant and\uddose-dependent, with a maximum 1.6-fold variation over sham.\udDNA damage was more pronounced in the presence of\udproteinase K, which is consistent with a major role for DNAprotein\udcrosslinks. In parallel, there was an increase of TBARS\ud(thiobarbituric acid reactive substances), which was statistically\udsignificant at the highest CS dose tested. No signs of apoptosis\udwere detectable by TUNEL method. These data show for the\udfirst time that exposure to CS produces a significant increase of\udlipid peroxidation products and DNA damage in the brain of\udmice exposed early in life. Especially taking into account the\udpoor ability of brain cells to repair DNA damage, these findings\udmay bear relevance in the pathogenesis of smoke-related\udneurodegenerative diseases