Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June 2013 Volume 5 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June 2013 Volume 5 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials

  • Authors:
    • Wen‑Ting Zhao
    • Yu‑Tian Wang
    • Zhao‑Wei Huang
    • Jing Fang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai 200031, P.R. China, Department of Gastroenterology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China
  • Pages: 1948-1954
    |
    Published online on: March 22, 2013
       https://doi.org/10.3892/ol.2013.1269
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The tumor suppressor gene breast cancer susceptibility gene 2 (BRCA2) is frequently mutated or epigenetically repressed in human cancer and has a significant role in the homologous recombination (HR) of DNA double‑strand breaks (DSBs). Although N‑nitrosodiethylamine (NDEA), N‑nitrosodiethanolamine (NDELA) and N‑nitrosodipropylamine (NDPA) have similar chemical structures and are able to induce DNA damage, they have varying carcinogenic risks. We hypothesized that the DNA damage repair pathways that are induced by these N‑nitroso compounds (NOCs) may differ and that this may contribute to the genotoxic‑carcinogenic effect of the NOCs. The present study aimed to characterize the formation of DSBs by NDEA, NDELA and NDPA and also to investigate whether BRCA2 is involved in the DNA damage response. The NOCs were observed to time‑dependently induce DSBs and the expression of γ‑H2AX in gastric cancer SGC7901 cells. It was observed that the DNA damage induced by NDEA, the most potent carcinogen, was not repaired as efficiently as that caused by NDELA or NDPA. The expression of BRCA2 and RAD51 was demonstrated to be inhibited by NDEA treatment but upregulated by NDELA or NDPA treatment. Furthermore, the knock down of BRCA2 expression impaired the DNA damage repair induced by NDELA or NDPA. The cells with this knock down exhibited an increased sensitivity to NDELA or NDPA treatment, but not to NDEA. These findings suggest that a BRCA2‑mediated pathway contributes to differential DSB repair and sensitivity in response to NOC exposure and that it may be associated with the genotoxic‑carcinogenic potential of NOCs.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Wooster R, Bignell G, Lancaster J, et al: Identification of the breast cancer susceptibility gene BRCA2. Nature. 378:789–792. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Tavtigian SV, Simard J, Rommens J, et al: The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 12:333–337. 1996. View Article : Google Scholar : PubMed/NCBI

3 

Jakubowska A, Nej K, Huzarski T, Scott RJ and Lubiński J: BRCA2 gene mutations in families with aggregations of breast and stomach cancers. Br J Cancer. 87:888–891. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Venkitaraman AR: Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 108:171–182. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Liede A, Karlan BY and Narod SA: Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 22:735–742. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Patel KJ, Yu VP, Lee H, et al: Involvement of Brca2 in DNA repair. Mol Cell. 1:347–357. 1998. View Article : Google Scholar : PubMed/NCBI

7 

Moynahan ME, Pierce AJ and Jasin M: BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell. 7:263–272. 2001. View Article : Google Scholar : PubMed/NCBI

8 

O’Donovan PJ and Livingston DM: BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis. 31:961–967. 2010.PubMed/NCBI

9 

Bryant HE, Schultz N, Thomas HD, et al: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 434:913–917. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Wang W and Figg WD: Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance. Cancer Biol Ther. 7:1004–1005. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Thompson LH and Schild D: Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res. 477:131–153. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Pellegrini L and Venkitaraman A: Emerging functions of BRCA2 in DNA recombination. Trends Biochem Sci. 29:310–316. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Shivji MK and Venkitaraman AR: DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2. DNA Repair (Amst). 3:835–843. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Ohnishi T, Mori E and Takahashi A: DNA double-strand breaks: their production, recognition, and repair in eukaryotes. Mutat Res. 669:8–12. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Davies AA, Masson JY, McIlwraith MJ, et al: Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell. 7:273–282. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Foster ER and Downs JA: Histone H2A phosphorylation in DNA double-strand break repair. FEBS J. 272:3231–3240. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Esashi F, Galkin VE, Yu X, et al: Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2. Nat Struct Mol Biol. 14:468–474. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Rogakou EP, Pilch DR, Orr AH, Ivanova VS and Bonner WM: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 273:5858–5868. 1998. View Article : Google Scholar : PubMed/NCBI

19 

van Attikum H, Fritsch O, Hohn B and Gasser SM: Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair. Cell. 119:777–788. 2004.PubMed/NCBI

20 

Pellegrini L, Yu DS, Lo T, et al: Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature. 420:287–293. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Powell SN and Kachnic LA: Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene. 22:5784–5791. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Filho PJ, Rios A, Valcárcel M and Caramao EB: Development of a new method for the determination of nitrosamines by micellar electrokinetic capillary chromatography. Water Res. 37:3837–3842. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Brambilla G and Martelli A: Genotoxic and carcinogenic risk to humans of drug-nitrite interaction products. Mutat Res. 635:17–52. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Hecht SS: Approaches to cancer prevention based on an understanding of N-nitrosamine carcinogenesis. Proc Soc Exp Biol Med. 216:181–191. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Williams GM, Iatropoulos MJ, Jeffrey AM, Luo FQ, Wang CX and Pittman B: Diethylnitrosamine exposure-responses for DNA ethylation, hepatocellular proliferation, and initiation of carcino-genesis in rat liver display non-linearities and thresholds. Arch Toxicol. 73:394–402. 1999. View Article : Google Scholar

26 

Pinto LF, Moraes E, Albano R, et al: Rat oesophageal cytochrome P450 (CYP) monooxygenase system: comparison to the liver and relevance in N-nitrosodiethylamine carcinogenesis. Carcinogenesis. 22:1877–1883. 2001. View Article : Google Scholar

27 

Visoni S, Lang M and Ribeiro Pinto LF: Hamster exhibits major differences in organ-specific metabolism of the esophageal carcinogen N-nitrosodiethylamine. Toxicol Lett. 183:90–94. 2008.PubMed/NCBI

28 

International Agency for Research on Cancer (IARC): Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum. Suppl 7:1–440. 1987.PubMed/NCBI

29 

International Agency for Research on Cancer (IARC): Some N-Nitroso Compounds. IARC Monogr Eval Carcinog Risks Hum. 17:1–365. 1978.

30 

International Agency for Research on Cancer (IARC): Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines. IARC Working Group Lyon, 23–30 October 1984. IARC Monogr Eval Carcinog Risk Chem Hum. 37:1–268. 1985.PubMed/NCBI

31 

Bradley MO, Dysart G, Fitzsimmons K, Harbach P, Lewin J and Wolf G: Measurements by filter elution of DNA single- and double-strand breaks in rat hepatocytes: effects of nitrosamines and gamma-irradiation. Cancer Res. 42:2592–2597. 1982.PubMed/NCBI

32 

Loeppky RN, Ye Q, Goelzer P and Chen Y: DNA adducts from N-nitrosodiethanolamine and related beta-oxidized nitrosamines in vivo: (32)P-postlabeling methods for glyoxal- and O(6)-hydroxyethyldeoxyguanosine adducts. Chem Res Toxicol. 15:470–482. 2002. View Article : Google Scholar

33 

Wiltshire T, Senft J, Wang Y, et al: BRCA1 contributes to cell cycle arrest and chemoresistance in response to the anticancer agent irofulven. Mol Pharmacol. 71:1051–1060. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Wang Y, Wiltshire T, Senft J, et al: Fanconi anemia D2 protein confers chemoresistance in response to the anticancer agent, irofulven. Mol Cancer Ther. 5:3153–3161. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Fillingham J, Keogh MC and Krogan NJ: GammaH2AX and its role in DNA double-strand break repair. Biochem Cell Biol. 84:568–577. 2006.PubMed/NCBI

36 

Dickey JS, Redon CE, Nakamura AJ, et al: H2AX: functional roles and potential applications. Chromosoma. 118:683–692. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Phillips ER and McKinnon PJ: DNA double-strand break repair and development. Oncogene. 26:7799–7808. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Hefferin ML and Tomkinson AE: Mechanism of DNA double-strand break repair by non-homologous end joining. DNA Repair (Amst). 4:639–648. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Schoenfeld AR, Apgar S, Dolios G, Wang R and Aaronson SA: BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol Cell Biol. 24:7444–7455. 2004. View Article : Google Scholar : PubMed/NCBI

40 

Philip S, Swaminathan S, Kuznetsov SG, et al: Degradation of BRCA2 in alkyltransferase-mediated DNA repair and its clinical implications. Cancer Res. 68:9973–9981. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao WT, Wang YT, Huang ZW and Fang J: BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials. Oncol Lett 5: 1948-1954, 2013.
APA
Zhao, W., Wang, Y., Huang, Z., & Fang, J. (2013). BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials. Oncology Letters, 5, 1948-1954. https://doi.org/10.3892/ol.2013.1269
MLA
Zhao, W., Wang, Y., Huang, Z., Fang, J."BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials". Oncology Letters 5.6 (2013): 1948-1954.
Chicago
Zhao, W., Wang, Y., Huang, Z., Fang, J."BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials". Oncology Letters 5, no. 6 (2013): 1948-1954. https://doi.org/10.3892/ol.2013.1269
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao WT, Wang YT, Huang ZW and Fang J: BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials. Oncol Lett 5: 1948-1954, 2013.
APA
Zhao, W., Wang, Y., Huang, Z., & Fang, J. (2013). BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials. Oncology Letters, 5, 1948-1954. https://doi.org/10.3892/ol.2013.1269
MLA
Zhao, W., Wang, Y., Huang, Z., Fang, J."BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials". Oncology Letters 5.6 (2013): 1948-1954.
Chicago
Zhao, W., Wang, Y., Huang, Z., Fang, J."BRCA2 affects the efficiency of DNA double‑strand break repair in response to N‑nitroso compounds with differing carcinogenic potentials". Oncology Letters 5, no. 6 (2013): 1948-1954. https://doi.org/10.3892/ol.2013.1269
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team