Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen–purine linkage in the differential global genomic repair propensity

Kathuria, Preetleen; Sharma, Purshotam; Wetmore, Stacey D.

doi:10.1093/nar/gkv701

Cited by 18 publications

(21 citation statements)

References 72 publications

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“…Exposure and subsequent metabolism (bioactivation) of AA lead to the formation of aristolactam AL-DNA adducts in urothelial tissue [ 87 , 88 ]. These bulky chemical DNA adducts were shown to be directly linked to A:T to T:A transversion mutations in TP53 in a study conducted by Grollman and colleagues [ 20 , 89 ]. There is significant evidence that AA is both a powerful nephrotoxic and carcinogenic agent with an extremely short latency period, not only in animals but also in humans [ 90 ].…”

Section: Urothelial Carcinoma and Aamentioning

confidence: 99%

Carcinogens and DNA damage

Barnes

Zubair

John

et al. 2018

Biochemical Society Transactions

240

126

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Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA–DNA or DNA–protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.

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Section: Urothelial Carcinoma and Aamentioning

confidence: 99%

Carcinogens and DNA damage

Barnes

Zubair

John

et al. 2018

Biochemical Society Transactions

240

126

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“…10 To compare the modified DNA structural features, the base step parameters at the modification site were calculated using a pseudostep consisting of the base pairs 5 and 3 with respect to the hydrophobic base pair. The use of pseudostep parameters rather than the traditional step parameters defined for adjacent base pairs in natural DNA 11 is justified since no protocol is currently available in the literature to calculate parameters of DNA steps involving hydrophobic bases. van der Waals stacking interaction energies between the hydrophobic and flanking base pairs were calculated using the "lie" command of cpptraj, whereas the percentage occupancies of hydrogen-bonding interactions within base pairs were calculated using the 'hbond' command of cpptraj.…”

Section: Table Of Contentsmentioning

confidence: 99%

How do hydrophobic nucleobases differ from natural DNA nucleobases? Comparison of structural features and duplex properties from QM calculations and MD simulations

Negi

Kathuria

Sharma

et al. 2017

Phys. Chem. Chem. Phys.

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Computational (DFT and MD simulation) methods are employed to systematically characterize the structural and energetic properties of five hydrophobic nucleobases (FEMO, MMO2, NaM, 5SICS and TPT3) that constitute four unnatural base pairs (FEMO:5SICS, MMO2:5SICS, NaM:5SICS and TPT3:NaM). These hydrophobic bases have been recently shown to be replicated when present between natural bases in DNA duplexes, with the highest replication fidelity and efficiency occuring for the TPT3:NaM pair. Our QM calculations suggest that the preferred (anti) glycosidic orientations of nucleosides containing hydrophobic bases are similar to the natural DNA nucleosides despite differences in their chemical structures. However, due to the inability to form interbase hydrogen bonds, hydrophobic base pairs intrinsically prefer nonplanar, distorted geometries, many of which are stabilized through π-π stacking interactions. Furthermore, the intrinsic stacking potential between a hydrophobic and a natural base is similar to that between two natural bases, indicating that the strength of stacking interactions in DNA duplexes containing hydrophobic bases is likely comparable to natural DNA. However, in contrast to the isolated base-pair geometries, our MD simulations suggest that the hydrophobic base pairs adopt variable geometries within DNA, which range from stacked (5SICS:FEMO) to nearly planar (5SICS:NaM and SICS:MMO2) to planar (TPT3:NaM). As a result, the duplex structural features at the site of modification depend on the identity of the hydrophobic base pair, where the TPT3:NaM pair causes the least structural changes compared to natural DNA. Overall, the structural insight obtained from our calculations on DNA containing hydrophobic base pairs explains the experimentally-observed higher fidelity and efficiency during replication of TPT3:NaM compared to other hydrophobic nucleobase pairs. By providing valuable structural information that explains the intrinsic and duplex properties of this class of unnatural nucleobases, the present work may aid the future design of improved hydrophobic analogues.

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“…In 2002, this research group reported a reductive activation of carcinogenic AAs by DT-diaphorase [56]. Nucleic Acids Research has published four relevant articles in recent years [57–60]. In 2015, Kathuria et al .…”

Section: Resultsmentioning

confidence: 99%

“…In 2015, Kathuria et al . published a study that utilized computational modeling to provide a plausible structural explanation for the experimentally observed differential global genome repair propensity of the ALII-N-2-dG and ALII-N-6-dA DNA adducts of AA II [60]. Finally, scientists are also interested in the exploration of the scientific significance of mutational signature induced by AA exposure; three related articles have been recently published in Science Translational Medicine magazine [1, 16, 61] (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Worldwide research trends on aristolochic acids (1957–2017): Suggestions for researchers

et al. 2019

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Aristolochic acids and their derivatives are components of many traditional medicines that have been used for thousands of years, particularly in Asian countries. To study the trends of research into aristolochic acids and provide suggestions for future study, we performed the following work. In this paper, we performed a bibliometric analysis using CiteSpace and HistCite software. We reviewed the three phases of the development of aristolochic acids by using bibliometrics. In addition, we performed a longitudinal review of published review articles over 60 years: 1,217 articles and 189 review articles on the history of aristolochic acid research published between 1957 and 2017 were analyzed. The performances of relevant countries, institutions, and authors are presented; the evolutionary trends of different categories are revealed; the history of research into aristolochic acids is divided into three phases, each of which has unique characteristics; and a roadmap of the historical overview of aristolochic acid research is finally established. Finally, five pertinent suggestions for future research into aristolochic acid are offered: (1) The study of the antitumor efficacy of aristolochic acids is of value; (2) The immune activity of aristolochic acids should be explored further; (3) Researchers should perform a thorough overview of the discovery of naturally occurring aristolochic acids; (4) More efforts should be directed toward exploring the correlation between aristolochic acid mutational signature and various cancers; (5) Further efforts should be devoted to the research and review work related to analytical chemistry. Our study is expected to benefit researchers in shaping future research directions.

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Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen–purine linkage in the differential global genomic repair propensity

Cited by 18 publications

References 72 publications

Carcinogens and DNA damage

Carcinogens and DNA damage

How do hydrophobic nucleobases differ from natural DNA nucleobases? Comparison of structural features and duplex properties from QM calculations and MD simulations

Worldwide research trends on aristolochic acids (1957–2017): Suggestions for researchers

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