Interaction of 2′-Deoxyadenosine with <i>cis</i>-2-Butene-1,4-dial: Computational Approach to Analysis of Multistep Chemical Reactions

Sviatenko, Liudmyla K.; Gorb, Leonid; Hovorun, Dmytro М.; Leszczyński, Jerzy

doi:10.1021/jp211911u

Cited by 12 publications

(27 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sviatenko et al. () applied quantum chemical computer assisted analysis to study the chemical interaction between BDA and dA. A similar technique was applied to study the interactions between BDA and dG (Sviatenko et al., ).…”

Section: Assessmentmentioning

confidence: 99%

“…Pluskota-Karwatka et al (2015) also mentioned that the BDA-dC adduct can be converted into deoxyuridine by loss of the adducted BDA and subsequent deamination. Sviatenko et al (2012) applied quantum chemical computer assisted analysis to study the chemical interaction between BDA and dA. A similar technique was applied to study the interactions between BDA and dG (Sviatenko et al, 2014).…”

Section: Binding To Dnamentioning

confidence: 99%

See 1 more Smart Citation

Risks for public health related to the presence of furan and methylfurans in food

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

View full text Add to dashboard Cite

The European Commission asked EFSA for a scientific evaluation on the risk to human health of the presence of furan and methylfurans (2-methylfuran, 3-methylfuran and 2,5-dimethylfuran) in food. They are formed in foods during thermal processing and can co-occur. Furans are produced from several precursors such as ascorbic acid, amino acids, carbohydrates, unsaturated fatty acids and carotenoids, and are found in a variety of foods including coffee and canned and jarred foods. Regarding furan occurrence, 17,056 analytical results were used in the evaluation. No occurrence data were received on methylfurans. The highest exposures to furan were estimated for infants, mainly from ready-to-eat meals. Grains and grain-based products contribute most for toddlers, other children and adolescents. In adults, elderly and very elderly, coffee is the main contributor to dietary exposure. Furan is absorbed from the gastrointestinal tract and is found in highest amounts in the liver. It has a short half-life and is metabolised by cytochrome P450 2E1 (CYP2E1) to the reactive metabolite, cis-but-2-ene-1,4-dialdehyde (BDA). BDA can bind covalently to amino acids, proteins and DNA. Furan is hepatotoxic in rats and mice with cholangiofibrosis in rats and hepatocellular adenomas/carcinomas in mice being the most prominent effects. There is limited evidence of chromosomal damage in vivo and a lack of understanding of the underlying mechanism. Clear evidence for indirect mechanisms involved in carcinogenesis include oxidative stress, gene expression alterations, epigenetic changes, inflammation and increased cell proliferation. The CONTAM Panel used a margin of exposure (MOE) approach for the risk characterisation using as a reference point a benchmark dose lower confidence limit for a benchmark response of 10% of 0.064 mg/kg body weight (bw) per day for the incidence of cholangiofibrosis in the rat. The calculated MOEs indicate a health concern. This conclusion was supported by the calculated MOEs for the neoplastic effects.

show abstract

Section: Assessmentmentioning

confidence: 99%

Section: Binding To Dnamentioning

confidence: 99%

Risks for public health related to the presence of furan and methylfurans in food

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

View full text Add to dashboard Cite

show abstract

“…Our previous studies have shed light on the mechanism of formation of dAdo-BDA adducts [8]. The current study describes the mechanism and kinetics of interaction of BDA with dGuo.…”

Section: Introductionmentioning

confidence: 84%

Interaction of 2'-deoxyguanosine with cis-2-butene-1,4-dial: Computational approach to analysis of multistep chemical reactions

et al. 2014

View full text Add to dashboard Cite

cis-2-Butene-1,4-dial represents a microsomal metabolite of furan, an industrially important chemical found in cigarette smoke, air pollution, and also in canned or jarred food. It is expected to be a human carcinogen. Aim. Investigation of an effect of cis-2-butene-1,4-dial on the 2'-deoxyguanosine which is a model of DNA site. Methods. Optimization of reaction species molecular structures, spectral parameters and Gibbs free energy calculations were performed using Gaussian09 program. Systems of differential equations for kinetics generation were solved using Mathcad15 program. Results. The predicted mechanism of the reaction of cis-2-butene-1,4dial with 2'-deoxyguanosine consists of four-step process formation of four diastereomeric primary adducts and further base-mediated five-step transformation of the primary adducts to the secondary one. The reaction kinetics, which allows defining the concentration change of any reaction species was calculated. Conclusions. Under physiological conditions the interaction between cis-2-butene-1,4-dial and 2'-deoxyguanosine leads to the formation of a stable adduct which could be responsible for the furan genotoxicity.

show abstract

“…Structures obtained after a 200 ns production run provide starting geometries bringing close together the Ap site and the offset purine forming the ICL identified by Gates et al. MD simulations were also performed with the open form of the abasic site over 200 ns, which albeit more rare is responsible for the ICL formation alongside a multi-step pathway (32). …”

Section: Methodsmentioning

confidence: 99%

Interstrand cross-linking implies contrasting structural consequences for DNA: insights from molecular dynamics

et al. 2016

View full text Add to dashboard Cite

Oxidatively-generated interstrand cross-links rank among the most deleterious DNA lesions. They originate from abasic sites, whose aldehyde group can form a covalent adduct after condensation with the exocyclic amino group of purines, sometimes with remarkably high yields. We use explicit solvent molecular dynamics simulations to unravel the structures and mechanical properties of two DNA sequences containing an interstrand cross-link. Our simulations palliate the absence of experimental structural and stiffness information for such DNA lesions and provide an unprecedented insight into the DNA embedding of lesions that represent a major challenge for DNA replication, transcription and gene regulation by preventing strand separation. Our results based on quantum chemical calculations also suggest that the embedding of the ICL within the duplex can tune the reaction profile, and hence can be responsible for the high difference in yields of formation.

show abstract

Interaction of 2′-Deoxyadenosine with cis-2-Butene-1,4-dial: Computational Approach to Analysis of Multistep Chemical Reactions

Cited by 12 publications

References 27 publications

Risks for public health related to the presence of furan and methylfurans in food

Risks for public health related to the presence of furan and methylfurans in food

Interaction of 2'-deoxyguanosine with cis-2-butene-1,4-dial: Computational approach to analysis of multistep chemical reactions

Interstrand cross-linking implies contrasting structural consequences for DNA: insights from molecular dynamics

Contact Info

Product

Resources

About