We have measured the yields of strand break formation and biological inactivation as a function of OH scavenger concentration for 60Co gamma-irradiated pBR322 plasmid and M13mp9 RF phage DNA. The yields of single-strand breaks (ssbs), double-strand breaks formed proportionally to dose (alpha dsbs), and lethal damage (LD) decrease with increasing scavenging capacity sigma, their ratios remaining approximately constant up to sigma approximately 10(8) s-1. On a double-logarithmic plot the yields decrease linearly with sigma in parallel lines. At higher scavenging capacities, the yields, while still decreasing, level off to a different extent. Our results for the yields of ssbs and alpha dsbs confirm those of Krisch et al. (1991) using SV40 DNA. The data were analysed assuming that DNA damage is brought about by OH radicals, and a non-scavengeable portion arising from the direct radiation effect. Using a model based on non-homogeneous scavenging kinetics, the dependence on scavenging capacity of the ssb yield could be quantitatively accounted for. From the scavenging dependence of the yield of dsbs which are formed quadratically with dose (beta dsbs) and which are the result of two independent ssbs within a critical distance h, a value of about 13 basepairs was obtained for h. The parallel decrease in the yield of ssbs and alpha dsbs with scavenging capacity was rationalized in terms of the Siddiqi-Bothe mechanism (Siddiqi and Bothe 1987). The efficiency of this mechanism was found to be approximately 0.01. From the analysis of the LD yields it was shown that up to sigma approximately 10(8) s-1, inactivation is predominantly due to single OH radicals which lead to LD with an efficiency of 0.12 per OH-induced ssb. At higher scavenging capacities, a non-scavengeable spur effect similar to the locally multiply damaged sites mechanism of Ward (1988) mainly contributes to LD.

Due to their beneficial nutritional profile the consumption of nuts contributes to a healthy diet and might reduce colon cancer risk. To get closer insights into potential mechanisms, the chemopreventive potential of different in vitro fermented nut varieties regarding the modulation of genes involved in detoxification (CAT, SOD2, GSTP1, GPx1) and cell cycle (p21, cyclin D2) as well as proliferation and apoptosis was examined in LT97 colon adenoma and primary epithelial colon cells. Fermentation supernatants (FS) of nuts significantly induced mRNA expression of CAT (up to 4.0-fold), SOD2 (up to 2.5-fold), and GSTP1 (up to 2.3-fold), while GPx1 expression was significantly reduced by all nut FS (0.8 fold on average). Levels of p21 mRNA were significantly enhanced (up to 2.6-fold), whereas all nut FS significantly decreased cyclin D2 expression (0.4-fold on average). In primary epithelial cells, expression of CAT (up to 3.5-fold), GSTP1 (up to 3.0-fold), and GPx1 (up to 3.9-fold) was increased, whereas p21 and cyclin D2 levels were not influenced. Nut FS significantly inhibited growth of LT97 cells and increased levels of early apoptotic cells (8.4% on average) and caspase 3 activity (4.6-fold on average), whereas caspase 3 activity was not modulated in primary colon cells. The differential modulation of genes involved in detoxification and cell cycle together with an inhibition of proliferation and induction of apoptosis in adenoma cells might contribute to chemopreventive effects of nuts regarding colon cancer.

No abstract

No abstract

These results indicate a chemopreventive potential of in vitro fermented hazelnuts which is largely unaffected by the roasting process.