Polyaromatic Hydrocarbons Cause Histone H2AX Phosphorylation in the S-phase of the Cell Cycle

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Author(s)

    • Shimohara Chiaki SHIMOHARA Chiaki
    • Environmental Genetics Laboratory, Frontier Science Innovation Center and Department of Biology, Graduate School of Science, Osaka Prefecture University
    • Sawai Tomoko SAWAI Tomoko
    • Environmental Genetics Laboratory, Frontier Science Innovation Center and Department of Biology, Graduate School of Science, Osaka Prefecture University
    • Yagi Takashi YAGI Takashi
    • Environmental Genetics Laboratory, Frontier Science Innovation Center and Department of Biology, Graduate School of Science, Osaka Prefecture University

Abstract

Phosphorylated histone H2AX (γH2AX) has been thought to be a marker of DNA double-strand breaks (DSBs). We examined whether polyaromatic hydrocarbons (PAH), benzo[a]pyrene, 1-nitropyrene, 1,8-dinitropyrene, 3-nitrobenzanthrone and <i>N</i>-hydroxy-3-aminobenzanthrone, can phosphorylate H2AX in human HeLa cells by using immunofluorescence microscopy. These substances do not cause DSB directly but produce purine adducts in cellular DNA. After exposure of the cells to these chemicals with a concentration giving 10% cell survival followed by incubation for one hour, γH2AX foci appeared in the cell nuclei. All cells expressing γH2AX corresponded to those that incorporated bromodeoxyuridine after PAH treatment, indicating that PAH-induced H2AX phosphorylation correlated to S-phase entry of the cells. Cells exposed to ultraviolet light and camptothecin, which produce pyrimidine dimers and single-strand breaks (SSBs) in DNA, respectively, showed the same response. On the other hand, cells exposed to X-ray and etoposide, which produce DSBs, expressed γH2AX not only in S-phase cells. These results suggest that H2AX phosphorylation signals are transmitted from directly produced DSBs in all cell phases as well as from DNA strand stalling in the S-phase. H2AX phosphorylation by all substances used in this experiment is inhibited by wortmannin, implying that H2AX phosphorylation is regulated by ATM and/or ATR pathways.<br>

Journal

  • Genes and Environment

    Genes and Environment 30(3), 92-99, 2008-08-20

    The Environmental Mutagen Society of Japan

References:  46

Cited by:  2

Codes

  • NII Article ID (NAID)
    110006873846
  • NII NACSIS-CAT ID (NCID)
    AA1212552X
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    18807046
  • NDL Article ID
    9628254
  • NDL Source Classification
    ZR1(科学技術--生物学)
  • NDL Call No.
    Z78-A397
  • Data Source
    CJP  CJPref  NDL  NII-ELS  J-STAGE 
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