4-Hydroxyestradiol Induces γ-H2AX in the Presence of an Inhibitor of Catechol-O-methyltransferase in Human Breast Cancer MCF-7 Cells

• Yamazaki Shunsuke

  Graduate School of Nutritional and Environmental Sciences, University of Shizuoka

• Sakakibara Hiroyuki

  Faculty of Agriculture, University of Miyazaki

• Takemura Hitomi

  Department of Home Economics, Aichi Gakusen University

• Shimoi Kayoko

  Global COE Program, University of Shizuoka Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka

書誌事項

タイトル別名

• 4-Hydroxyestradiol Induces γ-H2AX in the Presence of an Inhibitor of Catechol-<i>O</i>-methyltransferase in Human Breast Cancer MCF-7 Cells
• 4-Hydroxyestradiol Induces ^|^gamma;-H2AX in the Presence of an Inhibitor of Catechol-O-methyltransferase in Human Breast Cancer MCF-7 Cells

抄録

17β-Estradiol (E₂) is crucial for various physiological functions, such as in the development of the uterus and the mammary gland. However, prolonged exposure to E₂ is a risk factor for breast cancer. E₂ is metabolized to carcinogenic 4-hydroxyestradiol (4-OHE₂) and non-carcinogenic 2-hydroxyestradiol (2-OHE₂) by CYP1A1 and CYP1B1 in the breast tissue, respectively. These two catechol estrogens are converted to methylated metabolites by catechol-O-methyltransferase (COMT). 4-OHE₂ has been reported to be further oxidized to quinone intermediates which react with purine bases in DNA to form depurinating adducts, which generate highly mutagenic apurinic (AP) sites. Recently, phosphorylation of histone H2AX (γ-H2AX) has emerged as a sensitive marker for not only DNA double-strand breaks but also various types of DNA damage. 4-OHE₂-induced γ-H2AX in MCF-7 cells has never been reported yet. In this study, we investigated whether 4-OHE₂ induces γ-H2AX in response to DNA damage in the presence or absence of Ro 41-0960, an inhibitor of COMT, in human breast cancer MCF-7 cells. AP sites and γ-H2AX were induced 1-2 h after treatment with 4-OHE₂ and Ro 41-0960. The generation of intracellular reactive oxygen species (ROS) was also observed, as determined by 2′-7′-dichlorodihydrofluorescein diacetate fluorescence. By comparison, 2-OHE₂ and Ro 41-0960 had no effect on AP sites, γ-H2AX or the generation of ROS. KU-55933, an inhibitor of ataxia telangiectasia mutated (ATM), decreased the formation of γ-H2AX in conjunction with 4-OHE₂ and Ro 41-0960. These results demonstrate that 4-OHE₂, in the presence of Ro 41-0960, induces ATM-dependent γ-H2AX in MCF-7 cells.<br>

収録刊行物

• Genes and Environment

  Genes and Environment 34 (3), 129-135, 2012

  日本環境変異原学会

キーワード

• 4-hydroxyestradiol
• γ-H2AX
• catechol-<i>O</i>-methyltransferase
• apurinic sites

詳細情報

• CRID: 1390001205256126592
• NII論文ID: 10030688139
• NII書誌ID: AA1212552X
• DOI: 10.3123/jemsge.34.129
• COI: 1:CAS:528:DC%2BC38XhsVCjtbnF
• ISSN: 18807062
• ISSN: 18807046
• NDL書誌ID: 023880046
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023880046
• Web Site: https://search.jamas.or.jp/link/ui/2013323925
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可