Next Article in Journal
A Functional Interplay between IGF-1 and Adiponectin
Next Article in Special Issue
Around and beyond 53BP1 Nuclear Bodies
Previous Article in Journal
Inhibition of Starvation-Triggered Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in ARPE-19 Cells by Taurine through Modulating the Expression of Calpain-1 and Calpain-2
Previous Article in Special Issue
Induced Pluripotent Stem Cells: Advances in the Quest for Genetic Stability during Reprogramming Process
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(10), 2144; doi:10.3390/ijms18102144

DNA Adducts Formed by Aristolochic Acid Are Unique Biomarkers of Exposure and Explain the Initiation Phase of Upper Urothelial Cancer

1
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-12843 Prague 2, Czech Republic
2
Analytical and Environmental Sciences Division, MRC-PHE Centre for Environment and Health, King’s College London, London SE1 9NH, UK
3
NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King’s College London in partnership with Public Health England, London SE1 9NH, UK
4
Division of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 4 September 2017 / Revised: 29 September 2017 / Accepted: 11 October 2017 / Published: 14 October 2017
(This article belongs to the Special Issue DNA Injury and Repair Systems)
View Full-Text   |   Download PDF [1975 KB, uploaded 16 October 2017]   |  

Abstract

Aristolochic acid (AA) is a plant alkaloid that causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases frequently associated with upper urothelial cancer (UUC). This review summarizes the significance of AA-derived DNA adducts in the aetiology of UUC leading to specific A:T to T:A transversion mutations (mutational signature) in AAN/BEN-associated tumours, which are otherwise rare in individuals with UCC not exposed to AA. Therefore, such DNA damage produced by AA-DNA adducts is one rare example of the direct association of exposure and cancer development (UUC) in humans, confirming that the covalent binding of carcinogens to DNA is causally related to tumourigenesis. Although aristolochic acid I (AAI), the major component of the natural plant extract AA, might directly cause interstitial nephropathy, enzymatic activation of AAI to reactive intermediates capable of binding to DNA is a necessary step leading to the formation of AA-DNA adducts and subsequently AA-induced malignant transformation. Therefore, AA-DNA adducts can not only be utilized as biomarkers for the assessment of AA exposure and markers of AA-induced UUC, but also be used for the mechanistic evaluation of its enzymatic activation and detoxification. Differences in AA metabolism might be one of the reasons for an individual’s susceptibility in the multi-step process of AA carcinogenesis and studying associations between activities and/or polymorphisms of the enzymes metabolising AA is an important determinant to identify individuals having a high risk of developing AA-mediated UUC. View Full-Text
Keywords: aristolochic acid; carcinogenicity; mutagenesis; nephrotoxicity; DNA adduct formation aristolochic acid; carcinogenicity; mutagenesis; nephrotoxicity; DNA adduct formation
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Stiborová, M.; Arlt, V.M.; Schmeiser, H.H. DNA Adducts Formed by Aristolochic Acid Are Unique Biomarkers of Exposure and Explain the Initiation Phase of Upper Urothelial Cancer. Int. J. Mol. Sci. 2017, 18, 2144.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top