Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study

Background: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. Results: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ≥800 cigarette-years were 0.65 (95 % confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95 % CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorecta

Оценка надежности высоконадежных систем с учетом ЗИП

Предложены приближенные верхние и нижние оценки коэффициента готовности высоконадежной восстанавливаемой системы со структурной избыточностью. Полученные расчетные соотношения могут использоваться для оценки надежности высоконадежных систем с учетом различных стратегий пополнения ЗИП

Electrochemical Properties of Carbon Surfaces

Pretreatment of glassy carbon (GC) electrodes with 2-propanol, acetonitrile, or cyclohexane had a significant effect on electrode kinetics, adsorption, and capacitance. Reagent grade solvents slowed electron transfer rates for dopamine, ascorbic acid, Fe 3+/2+ , and Fe(CN) 6 3-/4-and decreased adsorption of anthraquinone-2,6-disulfonate (AQDS) and methylene blue (MB). However, if activated carbon (AC) was present in the solvent during pretreatment, the result was increased electron transfer rates and adsorption for several commonly studied redox systems. The large surface area of AC acts as a "getter" for solvent impurities and for species desorbed from the GC surface, leading to a carbon electrode surface with higher capacitance, higher adsorption of AQDS and MB, and faster electron-transfer rates for Fe(CN) 6 3-/4-, dopamine, and ascorbic acid. In addition, the treated surfaces were more reproducible, and aged electrodes were reactivated by AC in 2-propanol. The results imply that large, polar organic impurities are present on the polished GC surface which are removed by the combination of an organic solvent and activated carbon. These impurities contain oxygen detectable by XPS and appear to be weakly catalytic toward the Fe 3+/2+ redox system. The goal of understanding the factors which control electron transfer (ET) kinetics at carbon electrodes has remained elusive, despite the wide use of carbon electrodes and the extensive investigations of their electrochemical behavior. 1-5 A prerequisite to determining ET mechanisms at carbon electrodes is the preparation of reproducible and hopefully well-defined surfaces for which surface structure and electrochemical behavior may be correlated. However, the propensity of most carbon surfaces to oxidize and/or adsorb impurities leads to generally variable surface structures and accompanying variability in properties. A wide variety of surface preparations for carbon electrodes has been described, particularly for glassy carbon. [5][6][7][8][9][10][11][12] Depending on the application, surface preparation can be critical to performance, with apparently minor changes in procedure leading to large effects. In addition to practical considerations of reproducibility and stability, surface preparations bear heavily on the larger question of the relationship of surface structure and ET reactivity. To further complicate matters, results from several laboratories including our own have established that carbon surface properties can affect ET kinetics for different redox systems in very different ways. [13][14][15][16][17] For example, Ru(NH 3 ) 6 3+/2+ is fairly insensitive to surface preparation, with the observed heterogeneous ET rate constant (k°) varying by less than a factor of 10 for a wide range of surface modifications. In contrast, k°for Fe 3+/2+ in 0.2 M HClO 4 can vary by factors of 100-1000, due to catalysis by surface carbonyl groups. 14 Pretreatment procedures which dramatically affect ET kinetics for dopamine and ascorbic acid may have little effect on "outer-sphere" systems such as Ru(NH 3 ) 6 3+/2+ , IrCl 6 3-/2-, or Co(en) 3 3+/2+ . Therefore, several redox systems with different ET mechanisms should be considered when the effects of surface preparation techniques are examined. Previous reports from our laboratory have proposed systematic procedures for assessing surface variables which affect ET kinetics for particular redox systems. 5,14,17 Polishing is the most common preparation procedure for carbon electrodes, 4,12 particularly for glassy carbon (GC) and microdisk electrodes made from carbon fibers. During the process of developing chemical modifications for polished GC surfaces, we often noted large effects of organic solvent exposure on ET kinetics. It became apparent that understanding these solven