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Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

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Environmental Health and Preventive Medicine Aims and scope

Abstract

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 and32P-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 (H2O2)-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H2O2 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.

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Abbreviations

8-oxodG:

8-oxo-7,8-dihydro-2′-deoxyguanosine (also known as 8-hydroxy-2′-deoxyguanosine)

ROS:

reactive oxygen species

O2 − :

superoxide radical anion

OH:

hydroxyl radical

H2O2 :

hydrogen peroxide

1O2 :

singlet oxygen

HPLC-ECD:

electrochemical detector coupled to high-performance liquid chromatography

PG:

propyl gallate

GA:

gallic acid

BPA:

bisphenol-A

3-OH-BPA:

3-hydroxybisphenol A

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Authors and Affiliations

  1. Department of Environmental and Molecular Medicine, Mie University School of Medicine, Edobashi 2-174, 514-8507, Tsu, Mie, Japan

    Shinji Oikawa

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  1. Shinji Oikawa
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Correspondence to Shinji Oikawa.

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This article is based upon the research that was given Encouragement Award at the 74th Annual Meeting of the Japanese Society for Hygiene held in Tokyo, Japan on March 24–27, 2004.

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Oikawa, S. Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging. Environ Health Prev Med 10, 65–71 (2005). https://doi.org/10.1007/BF02897995

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