Dataset Information

Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

ABSTRACT: Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O(6)MeG adducts relative to its baseline by 21% (P < 0.01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P < 0.001) and HRM + HAMSB (P < 0.05) diets when compared with their respective baseline levels, but was lower following the HRM + HAMSB diet compared with the HRM diet (P < 0.05). Relative to its baseline, the HRM + HAMSB diet increased the excretion of SCFA by over 20% (P < 0.05) and increased the absolute abundances of the Clostridium coccoides group (P < 0.05), the Clostridium leptum group (P < 0.05), Lactobacillus spp. (P < 0.01), Parabacteroides distasonis (P < 0.001) and Ruminococcus bromii (P < 0.05), but lowered Ruminococcus torques (P < 0.05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P < 0.01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O(6)MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.

SUBMITTER: Le Leu RK

PROVIDER: S-EPMC4531472 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

Le Leu Richard K RK Winter Jean M JM Christophersen Claus T CT Young Graeme P GP Humphreys Karen J KJ Hu Ying Y Gratz Silvia W SW Miller Rosalind B RB Topping David L DL Bird Anthony R AR Conlon Michael A MA

The British journal of nutrition 20150617 2

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of ...[more]

PMID: 26084032

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Project description:O(6)-POB-dG (O(6)-[4-oxo-4-(3-pyridyl)but-1-yl]deoxyguanosine) are promutagenic nucleobase adducts that arise from DNA alkylation by metabolically activated tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonicotine (NNN). If not repaired, O(6)-POB-dG adducts cause mispairing during DNA replication, leading to G → A and G → T mutations. A specialized DNA repair protein, O(6)-alkylguanine-DNA-alkyltransferase (AGT), transfers the POB group from O(6)-POB-dG in DNA to a cysteine residue within the protein (Cys145), thus restoring normal guanine and preventing mutagenesis. The rates of AGT-mediated repair of O(6)-POB-dG may be affected by local DNA sequence context, potentially leading to adduct accumulation and increased mutagenesis at specific sites within the genome. In the present work, isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI(+)-MS/MS)-based methodology was developed to investigate the influence of DNA sequence on the kinetics of AGT-mediated repair of O(6)-POB-dG adducts. In our approach, synthetic DNA duplexes containing O(6)-POB-dG at a specified site are incubated with recombinant human AGT protein for defined periods of time. Following spiking with D(4)-O(6)-POB-dG internal standard and mild acid hydrolysis to release O(6)-POB-guanine (O(6)-POB-G) and D(4)-O(6)-POB-guanine (D(4)-O(6)-POB-G), samples are purified by solid phase extraction (SPE), and O(6)-POB-G adducts remaining in DNA are quantified by capillary HPLC-ESI(+)-MS/MS. The new method was validated by analyzing mixtures containing known amounts of O(6)-POB-G-containig DNA and the corresponding unmodified DNA duplexes and by examining the kinetics of alkyl transfer in the presence of increasing amounts of AGT protein. The disappearance of O(6)-POB-dG from DNA was accompanied by pyridyloxobutylation of AGT Cys-145 as determined by HPLC-ESI(+)-MS/MS of tryptic peptides. The applicability of the new approach was shown by determining the second order kinetics of AGT-mediated repair of O(6)-POB-dG adducts placed within a DNA duplex representing modified rat H-ras sequence (5'-AATAGTATCT[O(6)-POB-G]GAGCC-3') opposite either C or T. Faster rates of alkyl transfer were observed when O(6)-POB-dG was paired with T rather than with C (k = 1.74 × 10(6) M(-1) s(-1) vs 1.17 × 10(6) M(-1) s(-1)).

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Project description:Heterogeneity in meat food groups hinders interpretation of research regarding meat intake and chronic disease risk. Our objective was to investigate how heterogeneity in red meat (RM) and poultry food groups influences US population intake estimates. Based on a prior systematic review, we created an ontology of methods used to estimate RM [1= unprocessed RM; 2 (reference)= unprocessed RM + processed RM; 3= unprocessed RM + processed RM + processed poultry; and 4=unprocessed RM + processed RM + processed poultry + chicken patties/nuggets/tenders (PNT)] and three for poultry [A=unprocessed poultry; B= unprocessed poultry + PNT; C (reference)= unprocessed poultry + processed poultry + PNT). We applied methods to 2015-18 National Health and Nutrition Examination Survey data to estimate RM and poultry intake prevalence and amount. We estimated and compared intakes within RM and within poultry methods via the NCI Method for individuals ≥2 years old (n = 15,038), adjusted for age, sex, and race/Hispanic origin. We compared the population percentage that exceeded age- and sex-specific RM and poultry allotments from the Dietary Guidelines for Americans recommended eating patterns. The percent that consumed RM ranged from 47 ± 1.2% to 75 ± 0.8% across methods and mean amount ranged from 10.5 ± 0.28 to 18.2 ± 0.35 lean oz-equivalents/week; 38 ± 1.2% to 71 ± 0.7% and 9.8 ± 0.35 to 13.3 ± 0.35 lean oz-equivalents/week across poultry methods. Estimates for higher, but not lower, intake percentiles differed across RM methods. Compared to the reference, Method 1 was ≥3.0 oz-equivalents/week lower from 20th-70th percentiles, ≥6.0 oz-equivalents/week lower from 75th-90th percentiles, and ≥9.0 oz-equivalents/week lower for the 95th percentile. Method 4, but not Method 3, was ≥3.0 oz-equivalents/week higher than the reference from 50 to 95th percentiles. The population percentage that exceeded allotments was 27 ± 1.8% lower for Method 1, 9 ± 0.8% higher for Method 3, and 14 ± 0.9% higher for Method 4 compared to the reference. Differences were less pronounced for poultry. Our analysis quantifies the magnitude of bias introduced by heterogeneous meat food group methodology. Explicit descriptions of meat food groups are important for development of dietary recommendations to ensure that research studies are compared appropriately.

Dataset Information

Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

Publications

Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

Similar Datasets

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