In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.
Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD.
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Hironobu
H
Ikehata
Radioisotope Research Center, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
Toshio
T
Mori
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Masayuki
M
Yamamoto
D000818:Animals; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology*; D003596:Cytosine / Q000737:chemistry*; D003641:Deamination; D019281:Dimerization; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009154:Mutation; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D014466:Ultraviolet Rays
D003503:Cyclobutanes; D011743:Pyrimidines; D003596:Cytosine