Sequence-Specific DNA Damage by Reactive Oxygen Species : Implications for Carcinogenesis and Aging
スポンサーリンク
概要
- 論文の詳細を見る
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 ^<32>P-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 (H_2O_2)-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H_2O_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. 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. In this report, we show our experimental results and discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging.
- 日本衛生学会の論文
著者
-
Oikawa Shinji
Department Of Environmental And Molecular Medicine Mie University School Of Medicine
-
Oikawa Shinji
Department Of Environmental And Molecular Medicine Mie University Graduate School Of Medicine
-
OIKAWA Shinji
Department of Environmental and Molecular Medicine, Mie University School of Medicine
関連論文
- Expression of Human Metallothionein-2 in Escherichia coli: Cadmium Tolerance of Transformed Cells
- Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis
- DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect
- Distinct mechanisms of site-specific oxidative DNA damage by doxorubicin in the presence of copper(II) and NADPH-cytochrome P450,reductase
- S1-3 Role of oxidative DNA damage by environmental chemicals in carcinogenicity and reproductive toxicity.
- Mechanism of acceleration of telomere shortening by UVA
- Mechanism of Oxidative DNA Damage Induced by Environmental Carcinogens and Antioxidants
- Hydroxyurea Induces Site-specific DNA Damage via Formation of Hydrogen Peroxide and Nitric Oxide
- W-1-4 Role of sequence-specificity of DNA damage by oxidative stress(Theoretical and Experimental Approaches Relative to DNA Structure and DNA Damage Production, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
- Sequence-Specific DNA Damage by Reactive Oxygen Species : Implications for Carcinogenesis and Aging
- DNA damage and estrogenic activity induced by the environmental pollutant 2-nitrotoluene and its metabolite
- Oxidative DNA Damage in Relation to Neurotoxicity in the Brain of Mice Exposed to Arsenic at Environmentally Relevant Levels