Hostname: page-component-7c8c6479df-ph5wq Total loading time: 0 Render date: 2024-03-19T02:46:58.435Z Has data issue: false hasContentIssue false

The role of DNA damage as a therapeutic target in autosomal dominant polycystic kidney disease

Published online by Cambridge University Press:  26 November 2019

Jennifer Q. J. Zhang*
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
Sayanthooran Saravanabavan
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
Alexandra Munt
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
Annette T. Y. Wong
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
David C. Harris
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
Peter C. Harris
Affiliation:
Mayo Clinic Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN55905, USA
Yiping Wang
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
Gopala K. Rangan
Affiliation:
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, SydneyNSW2145, Australia Department of Renal Medicine, Westmead Hospital, SydneyNSW2145, Australia
*
Author for correspondence: Jennifer Q. J. Zhang, E-mail: jennifer.zhang@sydney.edu.au

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease and is caused by heterozygous germ-line mutations in either PKD1 (85%) or PKD2 (15%). It is characterised by the formation of numerous fluid-filled renal cysts and leads to adult-onset kidney failure in ~50% of patients by 60 years. Kidney cysts in ADPKD are focal and sporadic, arising from the clonal proliferation of collecting-duct principal cells, but in only 1–2% of nephrons for reasons that are not clear. Previous studies have demonstrated that further postnatal reductions in PKD1 (or PKD2) dose are required for kidney cyst formation, but the exact triggering factors are not clear. A growing body of evidence suggests that DNA damage, and activation of the DNA damage response pathway, are altered in ciliopathies. The aims of this review are to: (i) analyse the evidence linking DNA damage and renal cyst formation in ADPKD; (ii) evaluate the advantages and disadvantages of biomarkers to assess DNA damage in ADPKD and finally, (iii) evaluate the potential effects of current clinical treatments on modifying DNA damage in ADPKD. These studies will address the significance of DNA damage and may lead to a new therapeutic approach in ADPKD.

Type
Unsolicited Review
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Ong, ACM et al. (2015) Autosomal dominant polycystic kidney disease: the changing face of clinical management. The Lancet 385, 19932002.CrossRefGoogle ScholarPubMed
2.Lanktree, MB et al. (2018) Prevalence estimates of polycystic kidney and liver disease by population sequencing. Journal of the American Society of Nephrology 29, 25932600.CrossRefGoogle ScholarPubMed
3.Rangan, GK et al. (2016) Recent advances in autosomal-dominant polycystic kidney disease. Internal Medicine Journal 46, 883892.CrossRefGoogle ScholarPubMed
4.Porath, B et al. (2016) Mutations in GANAB, encoding the glucosidase IIalpha subunit, cause autosomal-dominant polycystic kidney and liver disease. American Journal of Human Genetics 98, 11931207.CrossRefGoogle ScholarPubMed
5.Cornec-Le Gall, E et al. (2018) Monoallelic mutations to DNAJB11 cause atypical autosomal-dominant polycystic kidney disease. American Journal of Human Genetics 102, 832844.CrossRefGoogle ScholarPubMed
6.Rangan, GK et al. (2015) Autosomal dominant polycystic kidney disease: a path forward. Seminars in Nephrology 35, 524.CrossRefGoogle ScholarPubMed
7.Chatterjee, S, Verma, SP and Pandey, P (2017) Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: a cross-species meta-analysis approach. Gene 627, 434450.CrossRefGoogle ScholarPubMed
8.Grantham, JJ, Geiser, JL and Evan, AP (1987) Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney International 31, 11451152.CrossRefGoogle ScholarPubMed
9.Grantham, JJ (2008) Autosomal dominant polycystic kidney disease. The New England Journal of Medicine 359, 14771485.CrossRefGoogle ScholarPubMed
10.Bae, KT et al. (2019) Growth pattern of kidney cyst number and volume in autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology 14, 823833.CrossRefGoogle ScholarPubMed
11.Lindahl, T and Barnes, DE (2000) Repair of endogenous DNA damage. Cold Spring Harbor Symposia on Quantitative Biology 65, 127133.CrossRefGoogle ScholarPubMed
12.Hoeijmakers, JHJ (2009) DNA damage, aging, and cancer. The New England Journal of Medicine 361, 14751485.CrossRefGoogle ScholarPubMed
13.Jackson, SP and Bartek, J (2009) The DNA-damage response in human biology and disease. Nature 461, 10711078.CrossRefGoogle ScholarPubMed
14.Kuo, LJ and Yang, LX (2008) γ-H2AX- A novel biomaker for DNA double-strand breaks. In Vivo 22, 305310.Google Scholar
15.Jena, NR (2012) DNA damage by reactive species: mechanisms, mutation and repair. Journal of Biosciences 37, 503517.CrossRefGoogle Scholar
16.Lindahl, T (1993) Instability and decay of the primary structure of DNA. Nature 362, 709715.CrossRefGoogle ScholarPubMed
17.Friedberg, EC, McDaniel, LD and Schultz, RA (2004) The role of endogenous and exogenous DNA damage and mutagenesis. Current Opinion in Genetics & Development 14, 510.CrossRefGoogle ScholarPubMed
18.De Bont, R and van Larebeke, N (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19, 169185.CrossRefGoogle ScholarPubMed
19.Birben, E et al. (2012) Oxidative stress and antioxidant defense. World Allergy Organization Journal 5, 919.CrossRefGoogle ScholarPubMed
20.O'Connor, MJ (2015) Targeting the DNA damage response in cancer. Molecular Cell 60, 547560.CrossRefGoogle Scholar
21.Lord, CJ and Ashworth, A (2012) The DNA damage response and cancer therapy. Nature 481, 287294.CrossRefGoogle ScholarPubMed
22.Christensson, A et al. (2013) Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years. International Journal of Cancer 133, 14521458.CrossRefGoogle Scholar
23.Wong, G et al. (2009) Association of CKD and cancer risk in older people. Journal of the American Society of Nephrology 20, 13411350.CrossRefGoogle ScholarPubMed
24.Cengiz, K et al. (1988) Sister chromatid exchange and chromosome abnormalities in uremic patients. Cancer Genetics and Cytogenetics 36, 5567.CrossRefGoogle ScholarPubMed
25.Sandoval, SB et al. (2012) Genomic instability in chronic renal failure patients. Environmental and Molecular Mutagenesis 53, 343349.CrossRefGoogle ScholarPubMed
26.Sandoval, SB et al. (2010) Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index. Mutagenesis 25, 603608.CrossRefGoogle ScholarPubMed
27.Vamvakas, S et al. (1996) Impairment of DNA repair in the course of long-term hemodialysis and under cyclosporine immunosuppression after renal transplantation. Transplantation Proceedings 28, 34683473.Google ScholarPubMed
28.Zevin, D et al. (1991) Impaired DNA repair in patients with end-stage renal disease and its improvement with hemodialysis. Mineral and Electrolyte Metabolism 17, 303306.Google ScholarPubMed
29.Small, DM et al. (2012) Oxidative stress, anti-oxidant therapies and chronic kidney disease. Nephrology 17, 311321.CrossRefGoogle ScholarPubMed
30.Sung, C-C et al. (2013) Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease. Oxidative Medicine and Cellular Longevity 2013, 115.CrossRefGoogle ScholarPubMed
31.Akagi, S et al. (2003) Significance of 8-hydroxy-2′-deoxyguanosine levels in patients with chronic renal failure. Nephrology 8, 192195.CrossRefGoogle ScholarPubMed
32.Martinez, JR and Grantham, JJ (1995) Polycystic kidney disease: etiology, pathogenesis, and treatment. Disease-a-Month 41, 693765.CrossRefGoogle ScholarPubMed
33.Lantinga-van Leeuwen, IS et al. (2004) Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Human Molecular Genetics 13, 30693077.CrossRefGoogle ScholarPubMed
34.Jiang, S-T et al. (2006) Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. American Journal of Pathology 168, 205220.CrossRefGoogle ScholarPubMed
35.Rossetti, S et al. (2009) Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney International 75, 848855.CrossRefGoogle ScholarPubMed
36.Hopp, K et al. (2012) Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. Journal of Clinical Investigation 122, 42574273.CrossRefGoogle ScholarPubMed
37.Grantham, JJ, Chapman, AB and Torres, VE (2006) Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clinical Journal of the American Society of Nephrology 1, 148.CrossRefGoogle ScholarPubMed
38.Calvet, JP (2008) Strategies to inhibit cyst formation in ADPKD. Clinical Journal of the American Society of Nephrology 3, 12051211.CrossRefGoogle ScholarPubMed
39.Harris, PC (2010) What is the role of somatic mutation in autosomal dominant polycystic kidney disease? Journal of the American Society of Nephrology 21, 10731076.CrossRefGoogle ScholarPubMed
40.Qian, F et al. (1996) The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 87, 979987.CrossRefGoogle ScholarPubMed
41.Brasier, JL and Henske, EP (1997) Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. Journal of Clinical Investigation 99, 194199.CrossRefGoogle ScholarPubMed
42.Wu, G et al. (1998) Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 93, 177188.CrossRefGoogle ScholarPubMed
43.Watnick, TJ et al. (1998) Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease. Molecular Cell 2, 247251.CrossRefGoogle ScholarPubMed
44.Pei, Y et al. (1999) Somatic PKD2 mutations in individual kidney and liver cysts support a ‘two-hit’ model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology 10, 15241529.Google ScholarPubMed
45.Koptides, M et al. (1999) Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease. Human Molecular Genetics 8, 509513.CrossRefGoogle ScholarPubMed
46.Takakura, A et al. (2008) Pkd1 inactivation induced in adulthood produces focal cystic disease. Journal of the American Society of Nephrology 19, 23512363.CrossRefGoogle ScholarPubMed
47.Tan, AY et al. (2018) Somatic mutations in renal cyst epithelium in autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology 29, 21392156.CrossRefGoogle ScholarPubMed
48.Takakura, A et al. (2009) Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Human Molecular Genetics 18, 25232531.CrossRefGoogle ScholarPubMed
49.Leonhard, WN et al. (2015) Scattered deletion of PKD1 in kidneys causes a cystic snowball effect and recapitulates polycystic kidney disease. Journal of the American Society of Nephrology 26, 13221333.CrossRefGoogle ScholarPubMed
50.Kenter, AT et al. (2019) Identifying cystogenic paracrine signaling molecules in cyst fluid of patients with polycystic kidney disease. American Journal of Physiology – Renal Physiology 316, F204F213.CrossRefGoogle ScholarPubMed
51.Johnson, CA and Collis, SJ (2016) Ciliogenesis and the DNA damage response: a stressful relationship. Cilia 5, 19.CrossRefGoogle ScholarPubMed
52.Attanasio, M (2015) Ciliopathies and DNA damage: an emerging nexus. Current Opinion in Nephrology and Hypertension 24, 366370.Google ScholarPubMed
53.Slaats, GG and Giles, RH (2015) Are renal ciliopathies (replication) stressed out? Trends in Cell Biology 25, 317319.CrossRefGoogle ScholarPubMed
54.Chaki, M et al. (2012) Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 150, 533548.CrossRefGoogle ScholarPubMed
55.Slaats, GG et al. (2014) Nephronophthisis-associated CEP164 regulates cell cycle progression, apoptosis and epithelial-to-mesenchymal transition. PLoS Genetics 10, e1004594.CrossRefGoogle ScholarPubMed
56.Torres, VE and Harris, PC (2006) Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases. Nature Clinical Practice Nephrology 2, 4055.CrossRefGoogle ScholarPubMed
57.Dmitrieva, NI, Cai, Q and Burg, MB (2004) Cells adapted to high NaCl have many DNA breaks and impaired DNA repair both in cell culture and in vivo. Proceedings of the National Academy of Sciences of the United States of America 101, 23172322.CrossRefGoogle ScholarPubMed
58.Smith, LA et al. (2006) Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human disease. Journal of the American Society of Nephrology 17, 28212831.CrossRefGoogle ScholarPubMed
59.Sohara, E et al. (2008) Nek8 regulates the expression and localization of polycystin-1 and polycystin-2. Journal of the American Society of Nephrology 19, 469476.CrossRefGoogle ScholarPubMed
60.Choi, H et al. (2013) NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies. Molecular Cell 51, 423439.CrossRefGoogle ScholarPubMed
61.Airik, R et al. (2014) Renal-retinal ciliopathy gene Sdccag8 regulates DNA damage response signaling. Journal of the American Society of Nephrology 25, 25732583.CrossRefGoogle ScholarPubMed
62.Cassini, MF et al. (2018) Mcp1 promotes macrophage-dependent cyst expansion in autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology 29, 24712481.CrossRefGoogle ScholarPubMed
63.Ta, MHT et al. (2016) Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats. World Journal of Nephrology 5, 339.CrossRefGoogle ScholarPubMed
64.Lecona, E and Fernández-Capetillo, O (2014) Replication stress and cancer: it takes two to tango. Experimental Cell Research 329, 2634.CrossRefGoogle ScholarPubMed
65.Liu, G et al. (2012) Replication fork stalling and checkpoint activation by a PKD1 locus mirror repeat polypurine-polypyrimidine (Pu-Py) tract. The Journal of Biological Chemistry 287, 3341233423.CrossRefGoogle ScholarPubMed
66.Lea, WA et al. (2018) Human-specific abnormal alternative splicing of wild-type PKD1 induces premature termination of polycystin-1. Journal of the American Society of Nephrology 29, 24822492.CrossRefGoogle ScholarPubMed
67.Li, M et al. (2013) Genomic instability in patients with autosomal-dominant polycystic kidney disease. Journal of International Medical Research 41, 169175.CrossRefGoogle ScholarPubMed
68.Battini, L et al. (2008) Loss of polycystin-1 causes centrosome amplification and genomic instability. Human Molecular Genetics 17, 28192833.CrossRefGoogle ScholarPubMed
69.Yu, T-M et al. (2016) Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study. The Lancet Oncology 17, 14191425.CrossRefGoogle ScholarPubMed
70.Cachat, F and Renella, R (2016) Risk of cancer in patients with polycystic kidney disease. The Lancet Oncology 17, e474.CrossRefGoogle ScholarPubMed
71.Chapman, JR and Wong, G (2016) Cancer in patients with inherited ciliopathies: polycystic kidney disease. The Lancet Oncology 17, 13431345.CrossRefGoogle ScholarPubMed
72.Wetmore, JB et al. (2014) Polycystic kidney disease and cancer after renal transplantation. Journal of the American Society of Nephrology 25, 23352341.CrossRefGoogle ScholarPubMed
73.Apeland, T, Holdaas, H and Mansoor, MA (2014) Kidney donors and kidney transplants have abnormal aminothiol redox status, and are at increased risk of oxidative stress and reduced redox buffer capacity. Clinical Biochemistry 47, 378382.CrossRefGoogle ScholarPubMed
74.Tariq, A et al. (2018) Systemic redox biomarkers and their relationship to prognostic risk markers in autosomal dominant polycystic kidney disease and IgA nephropathy. Clinical Biochemistry 56, 3340.CrossRefGoogle ScholarPubMed
75.Nowak, KL et al. (2018) Vascular dysfunction, oxidative stress, and inflammation in autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology 13, 14931501.Google ScholarPubMed
76.Woo, YM et al. (2014) Genome-wide methylation profiling of ADPKD identified epigenetically regulated genes associated with renal cyst development. Human Genetics 133, 281297.CrossRefGoogle ScholarPubMed
77.Woo, YM et al. (2015) Epigenetic silencing of the MUPCDH gene as a possible prognostic biomarker for cyst growth in ADPKD. Scientific Reports 5, 15238.CrossRefGoogle ScholarPubMed
78.Woo, YM et al. (2017) Profiling of miRNAs and target genes related to cystogenesis in ADPKD mouse models. Scientific Reports 7, 14151.CrossRefGoogle ScholarPubMed
79.Zawia, NH, Lahiri, DK and Cardozo-Pelaez, F (2009) Epigenetics, oxidative stress, and Alzheimer disease. Free Radical Biology and Medicine 46, 12411249.CrossRefGoogle ScholarPubMed
80.Pálmai-Pallag, T and Bachrati, CZ (2014) Inflammation-induced DNA damage and damage-induced inflammation: a vicious cycle. Microbes and Infection 16, 822832.CrossRefGoogle ScholarPubMed
81.Ta, MHT, Harris, DCH and Rangan, GK (2013) Role of interstitial inflammation in the pathogenesis of polycystic kidney disease: inflammation in polycystic kidney disease. Nephrology 18, 317330.CrossRefGoogle ScholarPubMed
82.Dmitrieva, NI, Bulavin, DV and Burg, MB (2003) High NaCl causes Mre11 to leave the nucleus, disrupting DNA damage signaling and repair. American Journal of Physiology – Renal Physiology 285, 266274.CrossRefGoogle Scholar
83.Schupp, N et al. (2007) Angiotensin II-induced genomic damage in renal cells can be prevented by angiotensin II type 1 receptor blockage or radical scavenging. American Journal of Physiology – Renal Physiology 292, F1427F1434.CrossRefGoogle ScholarPubMed
84.Schmid, U et al. (2008) Angiotensin II induces DNA damage in the kidney. Cancer Research 68, 92399246.CrossRefGoogle ScholarPubMed
85.Brand, S, Amann, K and Schupp, N (2013) Angiotensin II-induced hypertension dose-dependently leads to oxidative stress and DNA damage in mouse kidneys and hearts. Journal of Hypertension 31, 333344.CrossRefGoogle ScholarPubMed
86.Ma, Z et al. (2014) DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells. Biochimica et Biophysica Acta – Molecular Basis of Disease 1842, 10881096.CrossRefGoogle ScholarPubMed
87.Prasad, S et al. (2009) Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury. American Journal of Pathology 175, 14931503.CrossRefGoogle ScholarPubMed
88.Happé, H et al. (2009) Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Human Molecular Genetics 18, 25322542.CrossRefGoogle ScholarPubMed
89.Alexandrov, LB et al. (2015) Clock-like mutational processes in human somatic cells. Nature Genetics 47, 1402.CrossRefGoogle ScholarPubMed
90.Collins, AR (2004) The comet assay for DNA damage and repair. Molecular Biotechnology 26, 249.CrossRefGoogle ScholarPubMed
91.Schupp, N, Stopper, H and Heidland, A (2016) DNA damage in chronic kidney disease: evaluation of clinical biomarkers. Oxidative Medicine and Cellular Longevity 2016, 3592042.CrossRefGoogle ScholarPubMed
92.Sharma, A, Singh, K and Almasan, A (2012) Histone H2AX phosphorylation: a marker for DNA damage. In Bjergbæk, L (ed.), DNA Repair Protocols. Methods in Molecular Biology (Methods and Protocols), vol. 920. Totowa, New Jersey, USA: Humana Press, pp. 613626.Google Scholar
93.Bonner, WM et al. (2008) γH2AX and cancer. Nature Reviews Cancer 8, 957967.CrossRefGoogle ScholarPubMed
94.Mah, LJ, El-Osta, A and Karagiannis, TC (2010) γh2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 24, 679686.CrossRefGoogle ScholarPubMed
95.Siddiqui, MS et al. (2015) Persistent gamma H2AX: a promising molecular marker of DNA damage and aging. Mutation Research – Reviews in Mutation Research 766, 119.CrossRefGoogle Scholar
96.Yuan, J and Chen, J (2010) MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX. Journal of Biological Chemistry 285, 10971104.CrossRefGoogle ScholarPubMed
97.Valavanidis, A, Vlachogianni, T and Fiotakis, C (2009) 8-Hydroxy-2′-deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis & Ecotoxicology Reviews 27, 120139.CrossRefGoogle ScholarPubMed
98.Cooke, MS et al. (2009) Urinary 8-oxo-2′-deoxyguanosine – source, significance and supplements. Free Radical Research 32, 381397.CrossRefGoogle Scholar
99.Pilger, A and Rüdiger, HW (2006) 8-Hydroxy-2′-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures. International Archives of Occupational and Environmental Health 80, 115.CrossRefGoogle ScholarPubMed
100.Santella, RM (1999) Immunological methods for detection of carcinogen-DNA damage in humans. Cancer Epidemiology, Biomarkers & Prevention 8, 733739.Google ScholarPubMed
101.Figueroa-Gonzalez, G and Perez-Plasencia, C (2017) Strategies for the evaluation of DNA damage and repair mechanisms in cancer. Oncology Letters 13, 39823988.CrossRefGoogle Scholar
102.Schrier, RW et al. (2014) Blood pressure in early autosomal dominant polycystic kidney disease. The New England Journal of Medicine 371, 22552266.CrossRefGoogle ScholarPubMed
103.Brand, S et al. (2014) Oxidative DNA damage in kidneys and heart of hypertensive mice is prevented by blocking angiotensin II and aldosterone receptors. PLoS One 9, e115715.CrossRefGoogle ScholarPubMed
104.Torres, VE et al. (2017) Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrology, Dialysis, Transplantation 32, 12621262.CrossRefGoogle ScholarPubMed
105.Torres, VE et al. (2016) Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage: results from the TEMPO 3:4 Trial. Clinical Journal of the American Society of Nephrology 11, 803811.CrossRefGoogle ScholarPubMed
106.Wyatt, CM and Le Meur, Y (2018) REPRISE: tolvaptan in advanced polycystic kidney disease. Kidney International 93, 292295.CrossRefGoogle ScholarPubMed
107.Nazari, A et al. (2015) Vasopressin attenuates ischemia-reperfusion injury via reduction of oxidative stress and inhibition of mitochondrial permeability transition pore opening in rat hearts. European Journal of Pharmacology 760, 96102.CrossRefGoogle ScholarPubMed
108.Xiao, L-Y and Kan, W-M (2017) Cyclic AMP (cAMP) confers drug resistance against DNA damaging agents via PKAIA in CML cells. European Journal of Pharmacology 794, 201208.CrossRefGoogle ScholarPubMed
109.Faraco, G et al. (2014) Water deprivation induces neurovascular and cognitive dysfunction through vasopressin-induced oxidative stress. Journal of Cerebral Blood Flow & Metabolism 34, 852860.CrossRefGoogle ScholarPubMed
110.Takiar, V et al. (2011) Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proceedings of the National Academy of Sciences of the United States of America 108, 24622467.CrossRefGoogle ScholarPubMed
111.Chang, MY et al. (2017) Metformin inhibits cyst formation in a zebrafish model of polycystin-2 deficiency. Scientific Reports 7, 7161.CrossRefGoogle Scholar
112.Ohnishi, S, Mizutani, H and Kawanishi, S (2016) The enhancement of oxidative DNA damage by anti-diabetic metformin, buformin, and phenformin, via nitrogen-centered radicals. Free Radical Research 50, 929937.CrossRefGoogle ScholarPubMed
113.Amador, RR et al. (2012) Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells. Genetics and Molecular Biology 35, 153158.CrossRefGoogle ScholarPubMed
114.DeCensi, A et al. (2010) Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prevention Research 3, 14511461.CrossRefGoogle ScholarPubMed
115.Zakikhani, M et al. (2006) Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Research 66, 1026910273.CrossRefGoogle ScholarPubMed
116.Dowling, RJO et al. (2007) Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Research 67, 1080410812.CrossRefGoogle ScholarPubMed
117.Buzzai, M et al. (2007) Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Research 67, 67456752.CrossRefGoogle ScholarPubMed
118.Zakikhani, M et al. (2008) The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prevention Research 1, 369375.CrossRefGoogle ScholarPubMed
119.Othman, EM et al. (2016) Metformin protects kidney cells from insulin-mediated genotoxicity in vitro and in male Zucker diabetic fatty rats. Endocrinology 157, 548559.CrossRefGoogle ScholarPubMed
120.Najafi, M et al. (2018) Metformin: prevention of genomic instability and cancer: a review. Mutation Research – Genetic Toxicology and Environmental Mutagenesis 827, 18.CrossRefGoogle ScholarPubMed
121.Zhou, X et al. (2013) Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease. Journal of Clinical Investigation 123, 30843098.CrossRefGoogle ScholarPubMed
122.Surjana, D, Halliday, GM and Damian, DL (2010) Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. Journal of Nucleic Acids 2010, 157591.CrossRefGoogle ScholarPubMed
123.Chen, AC et al. (2015) A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. The New England Journal of Medicine 373, 16181626.CrossRefGoogle ScholarPubMed
124.Leonhard, WN et al. (2011) Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model. American Journal of Physiology – Renal Physiology 300, 11931202.CrossRefGoogle ScholarPubMed
125.Shang, H-S et al. (2016) Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells. Oncology Reports 36, 22072215.CrossRefGoogle ScholarPubMed
126.Cao, J et al. (2006) Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicological Sciences 91, 476483.CrossRefGoogle ScholarPubMed
127.Ting, C-Y et al. (2015) Curcumin triggers DNA damage and inhibits expression of DNA repair proteins in human lung cancer cells. Anticancer Research 35, 38673874.Google ScholarPubMed
128.Chen, X et al. (2017) Curcumin activates DNA repair pathway in bone marrow to improve carboplatin-induced myelosuppression. Scientific Reports 7, 17724–17711.CrossRefGoogle ScholarPubMed
129.Natoli, TA et al. (2010) Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nature Medicine 16, 788792.CrossRefGoogle ScholarPubMed
130.Torres, VE et al. (2011) Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology 6, 640647.CrossRefGoogle ScholarPubMed
131.Torres, VE et al. (2017) Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney International 91, 493500.CrossRefGoogle ScholarPubMed
132.Amro, OWMDMS et al. (2016) Low-Osmolar diet and adjusted water intake for vasopressin reduction in autosomal dominant polycystic kidney disease: a pilot randomized controlled trial. American Journal of Kidney Diseases 68, 882891.CrossRefGoogle ScholarPubMed
133.Warner, G et al. (2016) Food restriction ameliorates the development of polycystic kidney disease. Journal of the American Society of Nephrology 27, 14371447.CrossRefGoogle ScholarPubMed
134.Kipp, KR et al. (2016) A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. American Journal of Physiology – Renal Physiology 310, F726F731.CrossRefGoogle Scholar
135.Nowak, KL et al. (2017) Overweight and obesity Are predictors of progression in early autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology 29, 571578.CrossRefGoogle ScholarPubMed
136.Haley-Zitlin, V and Richardson, A (1993) Effect of dietary restriction on DNA repair and DNA damage. Mutation Research DNAging 295, 237245.CrossRefGoogle ScholarPubMed
137.Heydari, AR et al. (2007) Caloric restriction and genomic stability. Nucleic Acids Research 35, 74857496.CrossRefGoogle ScholarPubMed
138.Subba Rao, K (2003) Dietary calorie restriction, DNA-repair and brain aging. Molecular and Cellular Biochemistry 253, 313318.CrossRefGoogle Scholar
139.Vermeij, WP et al. (2016) Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature 537, 427431.CrossRefGoogle ScholarPubMed
140.Seliger, SL et al. (2018) A randomized clinical trial of metformin to treat autosomal dominant polycystic kidney disease. American Journal of Nephrology 47, 352360.CrossRefGoogle ScholarPubMed
141.Lu, H-F et al. (2009) Curcumin-induced DNA damage and inhibited DNA repair genes expressions in mouse-rat hybrid retina neuroblastoma cells ganglion cells (n18). Neurochemical Research 34, 14911497.CrossRefGoogle Scholar
142.Shayman, JA (2016) Targeting glycosphingolipid metabolism to treat kidney disease. Nephron 134, 3742.CrossRefGoogle ScholarPubMed
143.Shayman, JA (2018) Targeting glucosylceramide synthesis in the treatment of rare and common renal disease. Seminars in Nephrology 38, 183192.CrossRefGoogle ScholarPubMed
144.Deshmukh, GD et al. (1994) Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic (cpk/cpk) mouse. Journal of Lipid Research 35, 16111618.Google ScholarPubMed
145.Chatterjee, S et al. (1996) Role of lactosylceramide and MAP kinase in the proliferation of proximal tubular cells in human polycystic kidney disease. Journal of Lipid Research 37, 13341344.Google ScholarPubMed
146.Carroll, B, Donaldson, JC and Obeid, L (2015) Sphingolipids in the DNA damage response. Advances in Biological Regulation 58, 3852.CrossRefGoogle ScholarPubMed
147.Vit, J-P and Rosselli, F (2003) Role of the ceramide-signaling pathways in ionizing radiation-induced apoptosis. Oncogene 22, 86458652.CrossRefGoogle ScholarPubMed
148.Couto, D et al. (2016) New insights on non-enzymatic oxidation of ganglioside GM1 using mass spectrometry. Journal of the American Society for Mass Spectrometry 27, 19651978.CrossRefGoogle ScholarPubMed
149.Couto, D et al. (2015) Glycosphingolipids and oxidative stress: evaluation of hydroxyl radical oxidation of galactosyl and lactosylceramides using mass spectrometry. Chemistry and Physics of Lipids 191, 106114.CrossRefGoogle ScholarPubMed
150.Menezes, LF and Germino, GG (2015) Systems biology of polycystic kidney disease: a critical review. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 7, 3952.Google ScholarPubMed