-
Journal of Agricultural and Food... Jul 2013Nitrogen (N) fertilizer is used routinely in potato (Solanum tuberosum) cultivation to maximize yield. However, it also affects sugar and free amino acid concentrations...
Nitrogen (N) fertilizer is used routinely in potato (Solanum tuberosum) cultivation to maximize yield. However, it also affects sugar and free amino acid concentrations in potato tubers, and this has potential implications for food quality and safety because free amino acids and reducing sugars participate in the Maillard reaction during high-temperature cooking and processing. This results in the formation of color, aroma, and flavor compounds, but also some undesirable contaminants, including acrylamide, which forms when the amino acid that participates in the final stages of the reaction is asparagine. Another mineral, sulfur (S), also has profound effects on tuber composition. In this study, 13 varieties of potato were grown in a field trial in 2010 and treated with different combinations of N and S. Potatoes were analyzed immediately after harvest to show the effect of N and S fertilization on concentrations of free asparagine, other free amino acids, sugars, and acrylamide-forming potential. The study showed that N application can affect acrylamide-forming potential in potatoes but that the effect is type- (French fry, chipping, and boiling) and variety-dependent, with most varieties showing an increase in acrylamide formation in response to increased N but two showing a decrease. S application reduced glucose concentrations and mitigated the effect of high N application on the acrylamide-forming potential of some of the French fry-type potatoes.
Topics: Acrylamide; Amino Acids; Fertilizers; Glucose; Nitrogen; Plant Tubers; Solanum tuberosum; Sulfur
PubMed: 23768004
DOI: 10.1021/jf401570x -
The American Journal of Clinical... Oct 2022Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of...
BACKGROUND
Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited.
OBJECTIVES
This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status.
METHODS
This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors).
RESULTS
The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer.
CONCLUSIONS
Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.
Topics: Acrylamide; Breast Neoplasms; Carcinogens; Coffee; Cohort Studies; Diet; Dietary Exposure; Female; Hormones; Humans; Prospective Studies; Receptors, Estrogen; Risk Factors
PubMed: 36055962
DOI: 10.1093/ajcn/nqac167 -
Ecotoxicology and Environmental Safety Jun 2022Acrylamide is widely found in food as a side-product of high-temperature heating of starch-rich food. It has attracted much attention because of its neurotoxicity and...
BACKGROUND
Acrylamide is widely found in food as a side-product of high-temperature heating of starch-rich food. It has attracted much attention because of its neurotoxicity and carcinogenicity. However, the cancer risk and disease burden of dietary acrylamide exposure have not been quantified in China.
OBJECTIVE
To estimate the cancer risk and the disease burden attributable to dietary acrylamide exposure and quantify its health hazards.
METHOD
We first performed an exposure assessment of acrylamide in food, based on which the incremental excess lifetime cancer risk (ELCR) was calculated for cancer risk assessment. The DisMod Ⅱ software and the DALY calculator in R were used to calculate the disease burden due to dietary acrylamide exposure.
RESULTS
Average dietary acrylamide exposure in males was 0.1531 μg·kg·d and that in females was 0.1554 μg·kg·d, resulting in an ELCR of 7.81 × 10 for males and 7.92 × 10 for females in China. The dietary acrylamide exposure resulted in about 23,688.09 DALYs of cancers among the Chinese population in 2016, including 1331.93 DALYs of breast cancer, 243.32 DALYs of endometrial cancer, 248.91 DALYs of ovarian cancer, and 176.28 DALYs of kidney cancer, respectively.
CONCLUSION
The health hazards of dietary acrylamide exposure deserve attention. The burden of disease assessment could quantify the health hazards of food contaminants for prioritizing policies.
Topics: Acrylamide; China; Cost of Illness; Dietary Exposure; Female; Humans; Male; Neoplasms
PubMed: 35489291
DOI: 10.1016/j.ecoenv.2022.113551 -
Journal of the American Chemical Society Oct 2022Targeted protein degradation induced by heterobifunctional compounds and molecular glues presents an exciting avenue for chemical probe and drug discovery. To date,...
Targeted protein degradation induced by heterobifunctional compounds and molecular glues presents an exciting avenue for chemical probe and drug discovery. To date, small-molecule ligands have been discovered for only a limited number of E3 ligases, which is an important limiting factor for realizing the full potential of targeted protein degradation. We report herein the discovery by chemical proteomics of azetidine acrylamides that stereoselectively and site-specifically react with a cysteine (C1113) in the E3 ligase substrate receptor DCAF1. We demonstrate that the azetidine acrylamide ligands for DCAF1 can be developed into electrophilic proteolysis-targeting chimeras (PROTACs) that mediated targeted protein degradation in human cells. We show that this process is stereoselective and does not occur in cells expressing a C1113A mutant of DCAF1. Mechanistic studies indicate that only low fractional engagement of DCAF1 is required to support protein degradation by electrophilic PROTACs. These findings, taken together, demonstrate how the chemical proteomic analysis of stereochemically defined electrophilic compound sets can uncover ligandable sites on E3 ligases that support targeted protein degradation.
Topics: Acrylamide; Azetidines; Chimera; Cysteine; Humans; Intercellular Signaling Peptides and Proteins; Ligands; Proteolysis; Proteomics; Ubiquitin-Protein Ligases
PubMed: 36170674
DOI: 10.1021/jacs.2c08964 -
Journal of the American Chemical Society May 2023Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired,...
Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown to react with nucleophilic cysteines in the active site of purified enzymes. Here, we define the global cysteine reactivity and selectivity of a set of BDHI-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates that BDHIs capably engage reactive cysteine residues in the human proteome and the selectivity landscape of cysteines liganded by BDHI is distinct from that of haloacetamide electrophiles. Given its tempered reactivity, BDHIs showed restricted, selective engagement with proteins driven by interactions between a tunable binding element and the complementary protein sites. We validate that BDHI forms covalent conjugates with glutathione -transferase Pi (GSTP1) and peptidyl-prolyl - isomerase NIMA-interacting 1 (PIN1), emerging anticancer targets. BDHI electrophile was further exploited in Bruton's tyrosine kinase (BTK) inhibitor design using a single-step late-stage installation of the warhead onto acrylamide-containing compounds. Together, this study expands the spectrum of optimizable chemical tools for covalent ligand discovery and highlights the utility of 3-bromo-4,5-dihydroisoxazole as a cysteine-reactive electrophile.
Topics: Humans; Cysteine; Biological Products; Drug Discovery; Acrylamide; Catalytic Domain; NIMA-Interacting Peptidylprolyl Isomerase
PubMed: 37183434
DOI: 10.1021/jacs.3c00598 -
Molecules (Basel, Switzerland) Apr 2023The ability of additives to reduce the formation of acrylamide in simulated sugar cane syrups was investigated. Organic acids, B vitamins, and inorganic salts were added...
The ability of additives to reduce the formation of acrylamide in simulated sugar cane syrups was investigated. Organic acids, B vitamins, and inorganic salts were added individually and in combination to simulated thickened cane juice, and the mixtures were heated at 120 °C for 30 min. Calcium chloride (1%), citric acid (0.1%), and vitamin B3 (0.1%) were the most effective individual additives from each chemical family. The effects of CaCl (0-1%), citric acid (0-0.125%), and vitamin B3 (0-0.1125%), when added in combination, on the concentrations of acrylamide and hydroxymethylfurfural (HMF) were studied using a Box-Behnken design. Combinations of all three additives lowered the acrylamide production, but only the combination of citric acid and vitamin B3 had a significant synergistic effect. However, all these additives stimulated the production of HMF, and no significant interactive effect between pairs of additives on HMF production was observed. Calcium chloride stimulated the formation of HMF most strongly. These results indicate that certain combinations of these additives effectively reduce acrylamide formation, but they also lead to an increase in the formation of HMF in sugar syrup.
Topics: Saccharum; Acrylamide; Calcium Chloride; Furaldehyde; Niacinamide; Citric Acid
PubMed: 37049974
DOI: 10.3390/molecules28073212 -
Aging Clinical and Experimental Research Oct 2022Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic...
BACKGROUND
Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic fractures has been explored by a few cross-sectional studies.
AIMS
To investigate if dietary acrylamide is associated with the onset of fractures in North American participants at high risk/having knee osteoarthritis (OA), over 8 years of follow-up.
METHODS
A Cox's regression analysis, adjusted for baseline confounders was run and the data were reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Dietary acrylamide intake was assessed at the baseline using a food frequency questionnaire and categorized in tertiles (T), whilst fractures' history was recorded using self-reported information.
RESULTS
Altogether, 4,436 participants were included. Compared to participants with lower acrylamide intake (T1; < 3,313 μg), those with a higher acrylamide intake (T3; > 10,180 μg) reported a significantly higher risk of any fracture (HR = 1.37; 95% CI 1.12-1.68; p for trend = 0.009), forearm (HR = 1.73; 95% CI 1.09-2.77; p for trend = 0.04), spine (HR = 2.21; 95% CI 1.14-4.31; p for trend = 0.04), and hip fracture (HR = 4.09; 95% CI 1.29-12.96; p for trend = 0.046).
CONCLUSIONS
Our study is the first to report that high dietary acrylamide may be associated with an increased risk of osteoporotic fractures.
Topics: Humans; Osteoporotic Fractures; Acrylamide; Prospective Studies; Cross-Sectional Studies; Diet; Hip Fractures; Risk Factors
PubMed: 35962898
DOI: 10.1007/s40520-022-02214-9 -
Environmental Research Jan 2021Benzene and acrylamide are carcinogenic substances contained inter alia in tobacco smoke. The mercapturic acid metabolites of benzene, N-acetyl-S-phenyl-L-cysteine...
Benzene metabolite SPMA and acrylamide metabolites AAMA and GAMA in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).
Benzene and acrylamide are carcinogenic substances contained inter alia in tobacco smoke. The mercapturic acid metabolites of benzene, N-acetyl-S-phenyl-L-cysteine (SPMA), and of acrylamide, N-acetyl-S-(3-amino-3-oxopropyl)-cysteine (AAMA) and N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA), were analysed in 2260 first-morning void urine samples from children and adolescents aged 3-17 years, participating in the population-representative German Environmental Survey on Children and Adolescents, GerES V 2014-2017. SPMA was detected in 98% of the participants with a geometric mean (GM) of 0.097 μg/L urine. Smokers had about 10-fold higher levels of the benzene metabolite SPMA than non-smokers. The sample comprises of 48 self-reported smokers, mainly in the oldest age group (14-17-year-olds). Second-hand smoke exposure, living near busy or very busy roads, and using domestic fuels for heating were additionally associated with higher benzene metabolite levels. SPMA levels in GerES V were lower compared to levels found in other countries, which in part however may reflect different proportions of smokers. The acrylamide metabolites AAMA and GAMA were detected in 100% of the participants with a GM of 72.6 μg/L urine for AAMA and 15.0 μg/L urine for GAMA. Smoking children and adolescents had about 2.5-fold higher AAMA levels than non-smoking ones. The frequency of consumption of french-fried potatoes and potato crisps consumption was also positively associated with urinary AAMA and GAMA levels. Compared to the urinary AAMA and GAMA levels in Germany and other countries, levels in GerES V tended to be higher than in the few studies reported. The urinary levels of the benzene biomarker SPMA, and the acrylamide biomarkers AAMA and GAMA build the basis to derive reference values for the exposure of children and adolescents in Germany. The results reveal options for exposure reduction mainly in personal choices regarding smoking and diet, but also requiring policy to maintain efforts in non-smoking regulations and improving ambient air quality. Providing these results also to the European HBM Initiative HBM4EU will contribute to gain knowledge on the exposure of the European population, the health impact of carcinogens and thus providing support for substantiated exposure assessment.
Topics: Acetylcysteine; Acrylamide; Adolescent; Benzene; Biological Monitoring; Child; Child, Preschool; Environmental Monitoring; Germany; Humans
PubMed: 33065072
DOI: 10.1016/j.envres.2020.110295 -
Food Chemistry Apr 2017Acrylamide is produced from free asparagine and reducing sugars during high-temperature cooking and food processing, and potato products are major contributors to...
Acrylamide-forming potential of potatoes grown at different locations, and the ratio of free asparagine to reducing sugars at which free asparagine becomes a limiting factor for acrylamide formation.
Acrylamide is produced from free asparagine and reducing sugars during high-temperature cooking and food processing, and potato products are major contributors to dietary acrylamide intake. The present study analysed twenty varieties of potatoes grown at two sites (Doncaster and Woburn) in the United Kingdom to assess the effect of location of cultivation on acrylamide-forming potential. Analysis of variance revealed a full site by variety nested within type (French fry, boiling and crisping) by storage interaction for acrylamide (p<0.003, F-test), reducing sugars and total sugars (p<0.001, F-test). There was much greater free asparagine in potatoes grown at the Doncaster site compared with the Woburn site. Modelling of the relationship between the ratio of free asparagine to reducing sugars and the levels of acrylamide identified a value of 2.257±0.149 as the tipping point in the ratio below which free asparagine concentration could affect acrylamide formation.
Topics: Acrylamide; Amino Acids; Asparagine; Carbohydrates; Food Handling; Hot Temperature; Solanum tuberosum; United Kingdom
PubMed: 27855938
DOI: 10.1016/j.foodchem.2016.09.199 -
Frontiers in Public Health 2022The association between acrylamide exposure and the odds of developmental disabilities (DDs) is unclear. We conducted this analysis to explore whether acrylamide...
BACKGROUND
The association between acrylamide exposure and the odds of developmental disabilities (DDs) is unclear. We conducted this analysis to explore whether acrylamide exposure is related to DDs.
METHODS
We analyzed a sample of 1,140 children aged 6-17 years old from the US National Health and Nutrition Examination Survey 2013-2014 to 2015-2016. DDs were determined by reports of parents. Acrylamide exposure was evaluated by the hemoglobin adducts of acrylamide (HbAA) and its major metabolite glycidamide (HbGA). We investigated the association using binomial logistic regression analysis by taking HbAA and HbGA as continuous or quartile variables. Restricted cubic splines (RCS) were used to explore the non-linear relationship between HbAA or HbGA and the odds of DDs. Interaction analysis and propensity score matching (PSM) were used to validate the results.
RESULTS
A total of 134 participants were reported to have DDs. The median level of HbAA and HbGA was 41.6 and 40.5 pmol/g Hb, respectively. HbAA and HbGA were not associated with the odds of DDs when taken as continuous variables. When divided into quartiles, there was no evidence for a linear trend for HbAA and HbGA. RCS showed that there was a J-shaped association between HbGA and the odds of DDs ( for non-linearity, 0.023). The results were consistent in interaction analysis by age, gender, and race, and after PSM.
CONCLUSION
HbGA level was associated with the odds of DDs in a J-shaped manner among children. Further investigation is warranted to determine the causality and underlying mechanisms.
Topics: Acrylamide; Adolescent; Child; Cross-Sectional Studies; Developmental Disabilities; Hemoglobins; Humans; Nutrition Surveys
PubMed: 36249258
DOI: 10.3389/fpubh.2022.972368