Details

Autor(en) / Beteiligte

• Ikehata, Hironobu
• Mori, Toshio
• Kamei, Yasuhiro
• Douki, Thierry
• Cadet, Jean
• Yamamoto, Masayuki

Titel

Wavelength‐ and Tissue‐dependent Variations in the Mutagenicity of Cyclobutane Pyrimidine Dimers in Mouse Skin

Ist Teil von

• Photochemistry and photobiology, 2020-01, Vol.96 (1), p.94-104

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• The cyclobutane pyrimidine dimer (CPD) is a main mutagenic photolesion in DNA produced by UVR. We previously studied the wavelength‐dependent kinetics of mutation induction efficiency using monochromatic UVR sources and transgenic mice developed for mutation assay and established the action spectra of UVR mutagenicity in the mouse epidermis and dermis. Here, we further established the action spectra of CPD and pyrimidine(6‐4)pyrimidone photoproduct formation in the same tissues and in naked DNA using the same sources and mouse strain. Quantitative ELISA helped us estimate the photolesion formation efficiencies on a molecule‐per‐nucleotide basis. Using these action spectra, we confirmed that the UVR mutation mostly depends on CPD formation. Moreover, the mutagenicity of a CPD molecule (CPD mutagenicity) was found to vary by wavelength, peaking at approximately 313 nm in both the epidermis and dermis with similar wavelength‐dependent patterns. Thus, the CPD formation efficiency is a main determinant of UVR mutagenicity in mouse skin, whereas a wavelength‐dependent variation in the qualitative characteristics of CPD molecules also affects the mutagenic consequences of UVR insults. In addition, the CPD mutagenicity was always higher in the epidermis than in the dermis, suggesting different cellular responses to UVR between the two tissues irrespective of the wavelength. Although the efficiency of cyclobutane pyrimidine dimer (CPD) formation is a main determinant of UVR mutagenicity in mouse skin, the wavelength‐dependent variation in the qualitative characteristics of CPD molecules also affects the mutagenic consequences of UVR insults, as shown by the molecular mutagenicity of a CPD molecule, which exhibits a peak at approximately 313 nm. In addition, the CPD mutagenicity in the epidermis is always two‐ to three‐fold higher than that in the dermis irrespective of the wavelength.