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In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion.

ABSTRACT: Colorectal cancer (CRC) is the third most common cancer type in the world. Epidemiological research has demonstrated that both red and processed meat consumption significantly contribute to CRC risk. In this study, red meat toxicity was investigated by means of simulated gastrointestinal conditions, malondialdehyde (MDA) analysis and UHPLC-(HR)MS(/MS) based DNA adductomics. Since dairy products with high calcium content are associated with a decreased CRC-risk, the possible CRC-protective effects of calcium were assessed as well. The obtained results confirmed the earlier reported finding that heme-rich meat stimulates lipid peroxidation and O6-carboxymethylguanine (O6-CMG) DNA adduct formation during digestion. Calcium carbonate (CaCO3) supplementation resulted in both toxic and anti-toxic effects; i.e. stimulation of O6-CMG production, but reduction of MDA formation. DNA adductome mapping of meat digests revealed a significant interindividual variability. The observed DNA adduct profile also differed according to the digested meat type, uncovering different putative DNA adducts that seem to be associated with digestion of beef or chicken with or without supplemented CaCO3. Formamidopyrimidine-adenine was found to be discriminative for meat digests without added CaCO3, carboxyethylcytosine was significantly higher in beef digests and methoxymethylcytosine (or its hydroxyethylcytosine isomer) was found to be lower in meat digests supplemented with CaCO3. These results demonstrate that DNA adduct formation may be involved in the pathway that links red meat digestion to CRC promotion. In addition, the possible CRC-protective attributes of calcium through anti-oxidant actions could be documented.

SUBMITTER: Hemeryck LY

PROVIDER: S-EPMC6062164 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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<i>In vitro</i> DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion.

Hemeryck Lieselot Y LY Rombouts Caroline C Hecke Thomas Van TV Van Meulebroek Lieven L Bussche Julie Vanden JV De Smet Stefaan S Vanhaecke Lynn L

Toxicology research 20160622 5

Colorectal cancer (CRC) is the third most common cancer type in the world. Epidemiological research has demonstrated that both red and processed meat consumption significantly contribute to CRC risk. In this study, red meat toxicity was investigated by means of simulated gastrointestinal conditions, malondialdehyde (MDA) analysis and UHPLC-(HR)MS(/MS) based DNA adductomics. Since dairy products with high calcium content are associated with a decreased CRC-risk, the possible CRC-protective effect ...[more]

PMID: 30090439

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Project description:BackgroundReducing red meat is a strategy to improve public health and mitigate climate change in the United States and other high-income countries. Policies requiring warnings on the front of red meat packages are a promising intervention to shift consumers towards healthier and more sustainable food choices. We aimed to explore participants' reactions to health and environmental warning messages about red meat.MethodsBetween June and July 2020, we recruited a national convenience sample of US red meat consumers (n = 1,235; mean age 44 years) for an online survey. Participants were randomly assigned to one of four label conditions: no-label control, health warning, environment warning, and combined health and environment warning (both warnings shown side-by-side). Participants viewed three types of burritos (red meat [steak], chicken, and vegetarian) and selected their preferred item (primary outcome), the item they perceived to be most damaging to health, and the item they perceived to be most damaging to the environment (secondary outcomes). Participants then viewed their assigned warning on a series of other red meat products (no-label control participants were randomly re-assigned to one of the warning conditions) and rated the warnings on perceived message effectiveness, believability, negative emotions, perceived risk, attention, and learning something new. Finally, participants reported their intentions to reduce red meat consumption.ResultsThere were no significant differences in selection of the steak burrito between label conditions or in selection of the item most damaging to the environment. Those exposed to the health warning were more likely to select the steak burrito as most damaging to health compared to those exposed to other label conditions (health 73 %, combined 64 %, environment 60 %, no-label control 63 %, p < 0.05). The combined and health warnings elicited higher perceived message effectiveness ratings than the environment warning (combined mean 2.91, health 2.84, environment 2.61, p < 0.05).ConclusionsWarnings did not have a significant effect on item preference in the choice experiment. However, combined and health warnings performed better than the environment warning across a variety of warning label reaction measures. More research will be needed to understand whether warnings elicit behavioral change in real-world environments.Trial registrationAnalyses and hypotheses were preregistered on https://aspredicted.org/ph7mb.pdf on 23 June 2020.

Project description:Background:Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk. Objectives:The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity. Methods:A case-control study involving 521 both gender individuals, 253 centenarians (100.26 ± 1.98 years), and 268 controls (67.51 ± 3.25 years), low (LCR, n = 107) and high (HCR, n = 161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994, AGT-rs4762, AGR1-rs5182, GRK4-rs2960306, GRK4-rs1024323, NOS3-rs1799983, and SLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®. Results:Antilongevity factors consisted (OR 95% CI, p < 0.05) BMI 1.558 (1.445-1.680), hypertension 2.358 (1.565-3.553), smoking habits 4.528 (2.579-7.949), diabetes 5.553 (2.889-10.675), hypercholesterolemia 1.016 (1.010-1.022), and regular consumption of red meat 22.363 (13.987-35.755). Genetic aspects particularly for HCR individuals ACE II (OR: 3.96 (1.83-8.56), p < 0.0001) and NOS3 TT (OR: 3.11 (1.70-5.70), p < 0.0001) genotypes were also risk associate. Obesity, smoking, hypercholesterolemia, and frequent consumption of red meat have an additive action to hypertension in the longevity process. There was a synergistic interaction between the endothelial NOS3 genotypes and the severity of arterial hypertension. An epistatic interaction between functional genetic variants of GRK4 and angiotensinogen was also observed. Conclusions:Cardiovascular risk-related genetic and multifactorial or predominantly lifestyle aspects and its interactions might influence the aging process and contribute to exceptional longevity in Portuguese centenarians. Besides lifestyle, the activity of nitrite oxide synthase may be one of the main physiologic regulators of cardiovascular protection in the path of longevity.

Project description:PurposeTo determine the association between red meat (RM), processed red meat (PRM) and total red and processed red meat (TRPRM) consumption on nutritional adequacy and markers of health and cardio-metabolic diseases in British adults.MethodsIn this cross-sectional study of adults (19-64 y) from the National Diet and Nutrition Survey (NDNS) (n = 1758), RM and PRM consumption were assessed from 4 day estimated food diaries. Anthropometric measures, blood pressure (BP), pulse pressure (PP), plasma glucose, HbA1c, C-reactive protein, TAG, TC, LDL-C and HDL-C from the NDNS were used.Results43% of adults (men 57% and women 31%) consumed more than the 70 g/d TRPRM guidelines. Fewer adults in the highest tertile of TRPRM intake were below lower reference nutrient intakes (LRNIs), particularly for zinc and iron, respectively. In model 3 (controlled for age, energy intake, socioeconomic classification, number of daily cigarettes, BMI, dietary factors), higher RM consumption was associated with being significantly taller (model 3: P-ANCOVA = 0.006; P-T3/T1 = 0.0004) in men and lower diastolic BP (model 3: P-ANCOVA = 0.004; P-T3/T2 = 0.002) in women. Higher PRM in men was associated with significantly higher plasma ferritin concentration (model 3: P-ANCOVA = 0.0001; P-T2/T1 = 0.0001), being taller (P-ANCOVA = 0.019; P-T1/T2 = 0.047, T1/T3 = 0.044), increased body weight (model 3: P-ANCOVA = 0.001; P-T1/T3 = 0.0001), BMI (model 3: P-ANCOVA = 0.007; P-T1/T3 = 0.006) and smaller hip circumference (model 3: P-ANCOVA = 0.006; P-T3/T1 = 0.024; P-T2/T1 = 0.013) and in women significantly higher TC (model 3: P-ANCOVA = 0.020; P-T3/T2 = 0.016), LDL-C (P-ANCOVA = 0.030; P-T3/T2 = 0.025), HbA1c (model 3: P-ANCOVA = 0.0001; P-T2/T1 = 0.001; P-T3/T2 = 0.001) and higher PP (model 3: P-ANCOVA = 0.022; P-T3/T1 = 0.021). Higher PRM consumption was associated with significantly higher BMI and hip circumference in men, and higher TC, LDL-C, HbA1c and PP in women, which was not observed for RM consumption.

Dataset Information

In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion.

Publications

<i>In vitro</i> DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion.

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