Brca1 is involved in tolerance to adefovir dipivoxil‑induced DNA damage

  • Authors:
    • Hao Liu
    • Yang Wu
    • Fang He
    • Ziyuan Cheng
    • Zilu Zhao
    • Cuifang Xiang
    • Xiaoyu Feng
    • Xin Bai
    • Shunichi Takeda
    • Xiaohua Wu
    • Yong Qing
  • View Affiliations

  • Published online on: April 11, 2019     https://doi.org/10.3892/ijmm.2019.4164
  • Pages: 2491-2498
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Abstract

Nucleos(t)ide analogues (NAs) are currently the most important anti‑viral treatment option for patients with chronic hepatitis B (CHB). Adefovir dipivoxil (ADV), a diester pro‑drug of adefovir, has been widely used for the clinical therapy of hepatitis B virus infection. It has been previously reported that adefovir induced chromosomal aberrations (CAs) in the in vitro human peripheral blood lymphocyte assay, while the genotoxic mechanism remains elusive. To evaluate the possible mechanisms, the genotoxic effects of ADV on the TK6 and DT40 cell lines, as well as DNA repair‑deficient variants of DT40 cells, were assessed in the present study. A karyotype assay revealed ADV‑induced CAs, particularly chromosomal breaks, in wild‑type DT40 and TK6 cells. A γ‑H2AX foci formation assay confirmed the presence of DNA damage following treatment with ADV. Furthermore, Brca1‑/‑ DT40 cells exhibited an increased sensitivity to ADV, while the knockdown of various other DNA damage‑associated genes did not markedly affect the sensitivity. These comprehensive genetic studies identified the genotoxic capacity of ADV and suggested that Brca1 may be involved in the tolerance of ADV‑induced DNA damage. These results may contribute to the development of novel drugs against CHB with higher therapeutic efficacy and less genotoxicity.
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June 2019
Volume 43 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Liu, H., Wu, Y., He, F., Cheng, Z., Zhao, Z., Xiang, C. ... Qing, Y. (2019). Brca1 is involved in tolerance to adefovir dipivoxil‑induced DNA damage. International Journal of Molecular Medicine, 43, 2491-2498. https://doi.org/10.3892/ijmm.2019.4164
MLA
Liu, H., Wu, Y., He, F., Cheng, Z., Zhao, Z., Xiang, C., Feng, X., Bai, X., Takeda, S., Wu, X., Qing, Y."Brca1 is involved in tolerance to adefovir dipivoxil‑induced DNA damage". International Journal of Molecular Medicine 43.6 (2019): 2491-2498.
Chicago
Liu, H., Wu, Y., He, F., Cheng, Z., Zhao, Z., Xiang, C., Feng, X., Bai, X., Takeda, S., Wu, X., Qing, Y."Brca1 is involved in tolerance to adefovir dipivoxil‑induced DNA damage". International Journal of Molecular Medicine 43, no. 6 (2019): 2491-2498. https://doi.org/10.3892/ijmm.2019.4164