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Mutational signature of aristolochic acid: Clue to the recognition of a global disease.
- Source :
-
DNA repair [DNA Repair (Amst)] 2016 Aug; Vol. 44, pp. 205-211. Date of Electronic Publication: 2016 May 20. - Publication Year :
- 2016
-
Abstract
- Mutational signatures associated with specific forms of DNA damage have been identified in several forms of human cancer. Such signatures provide information regarding mechanisms of tumor induction which, in turn, can reduce exposure to carcinogens by shaping public health policy. Using a molecular epidemiologic approach that takes advantage of recent advances in genome sequencing while applying sensitive and specific analytical methods to characterize DNA damage, it has become increasingly possible to establish causative linkages between certain environmental mutagens and disease risk. In this perspective, we use aristolochic acid, a human carcinogen and nephrotoxin found in Aristolochia herbs, to illustrate the power and effectiveness of this multidisciplinary approach. The genome-wide mutational signature for this toxin, detected initially in cancers of the upper urinary tract, has subsequently been associated with cancers of the liver and kidney. These findings have significant implications for global public health, especially in China, where millions of individuals have used Aristolochia herbal remedies as part of traditional Chinese medicine and, thus, are at risk of developing aristolochic acid nephropathy and/or upper urinary tract carcinomas. The studies reported here set the stage for research into prevention and early detection, both of which will be required to manage a potentially devastating global disease.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Aristolochia chemistry
Aristolochia toxicity
Carcinoma chemically induced
Carcinoma diagnosis
Carcinoma epidemiology
DNA Adducts agonists
DNA Adducts biosynthesis
DNA Damage
DNA Repair
Genetic Predisposition to Disease
Humans
Kidney drug effects
Kidney metabolism
Kidney pathology
Liver drug effects
Liver metabolism
Liver pathology
Urinary Bladder drug effects
Urinary Bladder metabolism
Urinary Bladder pathology
Urologic Neoplasms chemically induced
Urologic Neoplasms diagnosis
Urologic Neoplasms epidemiology
Alkylating Agents toxicity
Aristolochic Acids toxicity
Carcinogens toxicity
Carcinoma genetics
Mutation
Urologic Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1568-7856
- Volume :
- 44
- Database :
- MEDLINE
- Journal :
- DNA repair
- Publication Type :
- Academic Journal
- Accession number :
- 27237586
- Full Text :
- https://doi.org/10.1016/j.dnarep.2016.05.027