2. Academic Validation
  3. Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage

Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage

  • Toxicol In Vitro. 2017 Aug;42:130-138. doi: 10.1016/j.tiv.2017.04.017.
Ying Liu 1,  Xiaohua Wu 2,  Xiaoqing Hu 1,  Ziyuan Chen 1,  Hao Liu 1,  Shunichi Takeda 3,  Yong Qing 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems of Education Ministry, West China School of Pharmacy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 2 Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems of Education Ministry, West China School of Pharmacy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: wuxh@scu.edu.cn.
  • 3 Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 4 Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems of Education Ministry, West China School of Pharmacy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: qingyong@scu.edu.cn.
PMID: 28431926 DOI: 10.1016/j.tiv.2017.04.017
Abstract

Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including Cancer. The Anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single strand break repair (SSBR) deficient cell lines of PARP1-/-, base excision repair (BER) deficient cell lines of Polβ-/-, homologous recombination (HR) mutants of Brca1-/- and Brca2-/- and translesion DNA synthesis (TLS) mutants of Rev3-/- and Rad18-/- were more sensitive to RSV. The sensitivities of cells were associated with enhanced DNA damage comparing the accumulation of γ-H2AX foci and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells. These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in response to RSV- induced genotoxicity.

Keywords

DNA damage; DNA repair; DT40; Genotoxicity; Resveratrol.

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