L R Ferguson

..We tested two TLR4 variants for association with IBD in the New Zealand caucasian population and assessed the cumulative evidence for association of TLR4 Asp299Gly and IBD...

..Human studies utilizing nutrigenomic/nutrigenetic technologies will be essential to quantifying and overcoming diet-related mutagenesis...

..New paradigms, possibly involving nutrigenomic tools, will be necessary to optimise the forms and levels of Se desirable for maximum protection of genomic stability in all humans...

..We did not find any evidence of association for MT genetic variation with CD. The lack of association indicates that genetic variants in the MT genes do not play a significant role in predisposing to CD in the New Zealand population...

..These methods have been successfully applied to animal models of Crohn's disease, and the time is right to move them to human studies...

..In particular, the incidence of malignant liver tumors and gastrointestinal tumors were significantly increased in the taro-fed group in comparison with the kumara group...

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..However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution...

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..New genomic technologies need to be matched with innovative methodologies to characterize the likely impact of foods and to take the field to another dimension of value for human diet development and optimized health...

..A combination of human correlation studies with experimental models could provide a rational strategy for optimising nutrigenetic approaches to IBD...

..DNA intercalation may serve to position other, chemically reactive molecules, in specific ways on the DNA, leading to a distinctive (and wider) range of mutagenic properties, and possible carcinogenic potential...

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..Furthermore, the data reveal that the observation of enhanced laxation and faecal bulking does not necessarily imply a reduction in carcinogen bioavailability...

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..Thus, providing they can reach effective levels in the colon, they could provide an important mechanism by which dietary fibres of food plants, such as spinach or cereal, protect against colon cancer...

..Providing the current data extrapolate to mammalian cells, they suggest that antimutagenic properties of hydroxycinnamic acids released from plant cell walls could play a role in dietary fibre protection against cancer...

..Since breakdown of normal mucosal antibacterial defence occurs in inflammatory bowel disease (IBD), variants in the DEFA5 gene could be associated with IBD risk...

..Jointly, these technologies can provide proof of human efficacy, and may be essential to ensure effective market transfer and uptake of broccoli and related foods...

..Because of the interdependence of epigenetic processes, combinations of these approaches may have maximum clinical efficacy...

..With improved methodologies for DNA sequencing and epigenetic changes, it is time to apply more sophisticated approaches to recognizing and proving the role of diet as a primary modulator of mutagenesis in humans...

..Such studies suggest nutrigenomic approaches to maintaining disease remission at present, and preventing disease development in the future...

..Adjusting the balance between meat and other dietary components may be critical to protecting against potential cancer risks...

..Carrying specific SNPs in this gene significantly modifies the risk of CD and/or UC in a New Zealand Caucasian population...

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..An even greater challenge may be in implementing population level changes in diet and behavior to fully exploit the potential of this field...

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..They are generally not point mutagens and may fail to provide distinctive fingerprints in mutation spectra. These characteristics may be limiting a realistic evaluation of their role in human carcinogenesis using current methodologies...

..The enhanced cancer incidence in the beta-carotene trial illustrates the potential benefit of utilising surrogate endpoints of malignant disease rather than incident cancer as a trial endpoint...

..Such experimental approaches might be expected to lead a better understanding of the interplay between different dietary factors and also between diet, hereditary and the environment...

..However, so far only a few animal carcinogenesis experiments have been reported using these materials, and no human intervention studies. We believe caution should be exercised in the addition of such materials to food...

..To provide an updated summary of dietary mutagens and their potential role in the etiology of cancer and atherosclerosis...

..More focused human studies are necessary before recommending specific polyphenolic supplements at specific doses in the human population...

..The results suggest that the bisbenzimidazole-linked mustard does cause alkylation and transcription blockage at novel DNA sites. in addition to sites characteristic of untargeted mustards...

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..More detailed population studies are warranted to establish the role of meat, meat processing, cooking methods and the interaction with food plants and/or with genotype and phenotype in New Zealand...

..The results indicate clear structure-activity relationships for the spectrum of mutagenic activity, which relate to both chain length and alkylator reactivity, for these compounds...

..However, the new definitions make it possible to increase "dietary fiber" without consuming any such materials. We suggest that this could have negative connotations for cancer risk in human populations...

..These data suggest very different modes of action between the DNA-targeted alkylators and their non-targeted counterparts...

..In contrast, the most chemically reactive compounds were the most toxic and most recombinogenic in yeast...

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..If this result extends to other compounds, experiments of this nature using the bacterial strains could provide a novel and useful screening system to identify hypoxia-selective cytotoxic anticancer drugs of potential clinical value...

..Leaves of the "hen and chickens" fern (Asplenium bulbiferum) contain antioxidant flavonoids such as kaempferol glucosides. Native seaweeds also have useful nutritive properties...

..The significant antitumor activity and low mutagenic potential shown by these compounds make them worthy of further study...

..This study examined associations between prostate cancer risk and 1) estimated daily intake of heterocyclic amines from cooked meat and 2) level of cooked-meat doneness...

..The possible relationship between adsorptive ability and ability of the bran from a particular species to protect against colorectal cancer is discussed...

..Of the compounds studied, the 4-OMe derivative appears to best retain the desirable antitumour properties of nitracrine while showing greatly-reduced mutagenic potential, and is an interesting lead for further development...

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..e. bacterial detection). There is evidence that carrying two SNPs in genes may lead to statistical significance for genes and SNPs that do not otherwise confirm as risk alleles for disease aetiology when analysed alone...

..Nutrigenomic approaches to dietary recommendations may be appropriate in this group...

..Both of these compounds were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. It would appear prudent to regard both of these compounds as potential human carcinogens...

..There was no evidence for an association with PTPN22...

..There is a danger that chemopreventive strategies developed using acute models may be misleading, since the mechanism is unlikely to occur during human dietary exposures...

..Given the current clinical data, this combination may be of more than theoretical interest...

..BLf caused significant reduction of faecal genotoxin-induced DNA damage in HT29 cells, and down-regulation of lipopolysaccharide (LPS)-induced macrophage cell stress and endotoxic response, in an infection status...

..Mutagenicity of topoisomerase-directed agents has been underestimated in the past, since these drugs are not usually capable of reacting covalently with DNA and usually have low mutagenicity in microbial assays...

..We suggest that podophyllin could potentiate these effects and question its continued widespread use...

..The results from this study support the accumulating evidence that suggests the 3p21 region is a CD-associated locus, although it remains unclear which is the causative SNP and/or gene...

..Mutations may provide at least part of the cause of enhanced susceptibility to chronic diseases associated with chronic inflammation...

..Here, we genotyped 50 IBD markers across 32 susceptibility genes in 9 commonly used gastrointestinal cell lines...

..We conclude that, in addition to strong evidence for genetic associations, factors likely to impact on immune response or reduce early exposure to microbes provide a main risk factor for CD in this New Zealand population...

..Subsequent studies might usefully consider complex mixtures and a battery of assays...

..We suggest that immunonutrition may provide a less invasive alternative to immunotherapy in protection against cancers associated with chronic inflammation...

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..It will be of interest to follow up CD patients carrying either JAK2 or STAT3 risk alleles for development of further secondary effects, including cancer...

..However, their mechanisms of action in humans are speculative, and research aimed at providing an integrated view of the gut microbiota and dietary fibre nutrition of humans needs to be developed...

..The aims of this study were to genotype these variants and correlate them to disease phenotype in New Zealand IBD patients...

..The wide range of detrimental items suggests that dietary maintenance of remission is likely to be difficult, and to exclude a substantial number of foods. Personalised diets may be especially important to these individuals...

..The second is in the application and further development of gene targeting approaches. These twin features will be addressed in this review in the context of modeling inflammatory bowel disease...

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..When the fractions were fed as a dietary supplement to rats and walls were isolated from the faeces, it was found that the pericarp walls were not degraded, but the aleurone walls were partially degraded...

..Recent developments with other minor groove binding small molecules and technological advances are also discussed...

..The failure to recognize the triallic nature of a SNP may lead to underestimations of real genetic associations...

..As complex disease is related to changes in gene expression, any variation in the human genome that alters gene expression is now a candidate for being involved in the disease process...

..Such screens provide a scientific basis for the rational choice of foods to be more rigorously investigated in animal models of IBD...

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..Dietary supplementation may provide an alternative approach...

..We speculate that lactic acid accumulation in patients with amoxapine overdose may be caused by loss of electron acceptor activity in tissues...

..We conclude that changes in activity and expression of xenobiotic metabolising enzymes could play a role in the contrasting effects of these two types of dietary fibre on carcinogen uptake and disposition...

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..There is increasing reason to believe that the long-term use of a combination of anticarcinogens, over an extended time span, may provide a realistic prospect of reducing the current burden of human cancers...

..It also raises the question as to whether glutathione peroxidase saturation levels are appropriate indicators of the optimal selenium levels for a given population...

..It is concluded that the periderm cell walls contain covalently bound anthocyanidin-containing compounds, possibly anthocyanins...

..In contrast, the longer chain length targeted mustards, which form >90% of initial adducts at adenine N(1) sites, generated also formed transversion mutations, but these overwhelmingly (24/27) involved AT base pairs...

..New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches...

..Exploring these different mechanisms of apoptosis may provide new directions for the development of antitumor drugs...

..These metabolite differences may be associated with residual genes from the embryonic stem cells of the 129P2 mouse strain that were used to create the IL10(-/-) mouse, or may indicate novel functions of IL10 unrelated to inflammation...

..This study demonstrates that nontargeted GCMS metabolite profiling of IL10-/- mice can provide insights into the metabolic effects of IL10-deficiency and identify potential markers of intestinal inflammation...

..In contrast, 6 mo of selenium supplementation did not affect GPx activity. This study presents, to our knowledge for the first time, both measurements of human hemolysate TR activity and its relation to serum selenium...

..Thus, the aqueous extract of kiwifruit puree containing health-beneficial constituents can be considered a functional ingredient for gluten-free bread formulation...

..Several of the compounds showed in vitro HDAC inhibition ability in PC3, HCT116 and NIH-3T3 cell lines comparable to that of SAHA...

..g., haplotype of GGC was 2.9-fold more in the CD or UCpatients) or decrease (e.g., TGT was 0.47-fold less in UC patients) the risk of IBD in a New Zealand Caucasian population...

..Such training will widen public understanding, and permit dialogue with regulatory officials to responsibly develop, apply and progress this new field...

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..Our study indicates that Citrus Pectin and Oligofructose, but not Cellulose, can significantly increase indices of folate status in rats and lower tHcy. It also confirms the ability of the large bowel to absorb folate...

..The results are interpreted with respect to intercalation, steric interactions, effects of base strength on DNA binding, enzymatic processing, and a slipped mispairing model of frameshift mutagenesis...