UVA1 genotoxicity is mediated not by oxidative damage but by cyclobutane pyrimidine dimers in normal mouse skin

Hironobu Ikehata, Kazuaki Kawai, Jun Ichiro Komura, Ko Sakatsume, Liangcheng Wang, Masaru Imai, Shoichi Higashi, Osamu Nikaido, Kazuo Yamamoto, Kotaro Hieda, Masakatsu Watanabe, Hiroshi Kasai, Tetsuya Ono

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

UVA1 induces the formation of 8-hydroxy-2′-deoxyguanosines (8-OH-dGs) and cyclobutane pyrimidine dimers (CPDs) in the cellular genome. However, the relative contribution of each type of damage to the in vivo genotoxicity of UVA1 has not been clarified. We irradiated living mouse skin with 364-nm UVA1 laser light and analyzed the DNA damage formation and mutation induction in the epidermis and dermis. Although dose-dependent increases were observed for both 8-OH-dG and CPD, the mutation induction in the skin was found to result specifically from the CPD formation, based on the induced mutation spectra in the skin genome: the dominance of C → T transition at a dipyrimidine site. Moreover, these UV-specific mutations occurred preferentially at the 5′-TCG-3′ sequence, suggesting that CpG methylation and photosensitization-mediated triplet energy transfer to thymine contribute to the CPD-mediated UVA1 genotoxicity. Thus, it is the CPD formation, not the oxidative stress, that effectively brings about the genotoxicity in normal skin after UVA1 exposure. We also found differences in the responses to the UVA1 genotoxicity between the epidermis and the dermis: the mutation induction after UVA1 irradiation was suppressed in the dermis at all levels of irradiance examined, whereas it leveled off from a certain high irradiance in the epidermis.

Original languageEnglish
Pages (from-to)2289-2296
Number of pages8
JournalJournal of Investigative Dermatology
Volume128
Issue number9
DOIs
Publication statusPublished - 2008 Sep

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'UVA1 genotoxicity is mediated not by oxidative damage but by cyclobutane pyrimidine dimers in normal mouse skin'. Together they form a unique fingerprint.

Cite this