Sequence-Specific DNA Damage by Reactive Oxygen Species: Implications for Carcinogenesis and Aging

• OIKAWA Shinji

  Department of Environmental and Molecular Medicine, Mie University School of Medicine

抄録

Reactive oxygen species (ROS) generated by environmental chemicals can cause sequence-specific DNA damage, which may lead to carcinogenesis and aging. We investigated the mechanism of DNA damage by environmental chemicals (catechol, propyl gallate and bisphenol-A), homocysteine and UVA radiation using human cultured cell lines and ³²P-labeled DNA fragments. Carcinogenic catechol induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II) and NADH. Furthermore, catechol increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, but not in HP100, a hydrogen peroxide (H₂O ₂)-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H₂O ₂ plays an important role in the carcinogenic process of catechol. In addition, an environmental factor, bisphenol-A, and a dietary factor, propyl gallate, also induced sequence-specific DNA damage via ROS generation.<br> UVA, as well as UVB, contributes to photoaging. In humans, telomere shortening is believed to be associated with cell senescence. In this study, we investigated the shortening rate of telomeres in human WI-38 fibroblasts exposed to UVA irradiation. The telomere length (as measured by terminal restriction fragment length) in WI-38 fibroblasts irradiated with UVA decreased with increasing the irradiation dose. UVA irradiation with riboflavin caused damage specifically at the GGG sequence in the DNA fragments containing telomere sequence (TTAGGG)₄. We concluded that the GGG-specific damage in telomere sequence induced by UVA irradiation participates in the increase of the telomere shortening rate.<br> In this report, we show our experimental results and discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging.<br>

収録刊行物

• Environmental Health and Preventive Medicine

  Environmental Health and Preventive Medicine 10 (2), 65-71, 2005

  一般社団法人日本衛生学会

キーワード

• DNA damage
• reactive oxygen species
• 8-oxo-7
• 8-dihydro-2'-deoxyguanosine
• carcinogenesis
• aging

詳細情報

• CRID: 1390282679434402048
• NII論文ID: 110002703949
• NII書誌ID: AA1108348X
• DOI: 10.1265/ehpm.10.65
• ISSN: 13474715
• ISSN: 1342078X
• Web Site: https://search.jamas.or.jp/link/ui/2006193091
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可