Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke (Department of Environmental and Molecular Medicine, Mie University School of Medicine) ;
  • Oikawa, Shinji (Department of Environmental and Molecular Medicine, Mie University School of Medicine) ;
  • Hiraku, Yusuke (Department of Environmental and Molecular Medicine, Mie University School of Medicine)
  • Published : 2002.08.01

Abstract

Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.

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