Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Influence of prophylaxis paste treatment on the abrasive wear of surface sealants

OBJECTIVE: To investigate the abrasive wear of surface sealants (Seal&Protect and K-0184 (experimental sealant)) and the influence of pre-treatment with mineral deposit forming prophylaxis pastes (NUPRO Sensodyne and NUPRO) on this wear. METHODS: One hundred and eight bovine dentine samples were randomly allocated to nine groups (1-9). Pre-treatment (10 s): groups 1-3: untreated, groups 4-6: NUPRO, groups 7-9: NUPRO Sensodyne. Sealing: groups 1, 4 and 7: unsealed, groups 2, 5 and 8: Seal&Protect, groups 3, 6 and 9: K-0184 (experimental sealer). Samples were then brushed with 12 000 brushing strokes (BS) with toothpaste slurry in an automatic brushing machine (120 BS/min; F = 2.5 N). Surface profiles were recorded at baseline, after pre-treatment and sealing and after each 2000 BS. RESULTS: Total profile change (wear or gain due to pre-treatment, treatment and 12 000 BS): groups 1, 4 and 7 (no surface sealant) showed a not significantly different wear of 18.48 ± 2.63 µm, 24.98 ± 3.02 µm and 21.50 ± 5.47 µm, respectively. Remaining groups (sealed) showed a gain in height with no significant difference among each other. Wear in sealed groups (2, 3, 5, 6, 8 and 9) were not significantly different at all numbers of brushing strokes. Starting with 4000 BS, the wear in unsealed groups (1, 4 and 7) was statistically significantly higher compared to all other groups. CONCLUSION: Stability and wear resistance of surface sealants are not affected by pre-treatment of dentine with NUPRO Sensodyne. The surface sealants tested provide a stable protective surface layer on dentine, which lasts for at least 12 000 brushing strokes

AGN Feedback in Elliptical Galaxies: Numerical Simulations

The importance of feedback (radiative and mechanical) from massive black holes at the centers of elliptical galaxies is not in doubt, given the well established relation among black hole mass and galaxy optical luminosity. Here, with the aid of high-resolution hydrodynamical simulations, we discuss how this feedback affects the hot ISM of isolated elliptical galaxies of different mass. The cooling and heating functions include photoionization plus Compton heating, the radiative transport equations are solved, and the mechanical feedback due to the nuclear wind is also described on a physical basis; star formation is considered. In the medium-high mass galaxies the resulting evolution is highly unsteady. At early times major accretion episodes caused by cooling flows in the recycled gas produced by stellar evolution trigger AGN flaring: relaxation instabilities occur so that duty cycles are small enough to account for the very small fraction of massive ellipticals observed to be in the QSO-phase, when the accretion luminosity approaches the Eddington luminosity. At low redshift all models are characterized by smooth, very sub-Eddington mass accretion rates. The mass accumulated by the central black hole is limited to range observed today, even though the mass lost by the evolving stellar population is roughly two order of magnitude larger than the black hole masses observed in elliptical galaxies.Comment: 20 pages, 4 (low-resolution) figures. Abbreviated version of the article to appear in book "Hot Interstellar Matter in Elliptical Galaxies", D.-W. Kim and S. Pellegrini eds., Astrophysics and Space Science Library (ASSL), Springe