UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?
The carcinogenic action of UVA radiation is commonly attributed to DNA oxidation mediated by endogenous photosensitisers. Yet, it was recently shown that cyclobutane pyrimidine dimers (CPD), well known for their involvement in UVB genotoxicity, are produced in larger yield than oxidative lesions in UVA-irradiated cells and skin. In the present work, we gathered mechanistic information on this photoreaction by comparing formation of all possible bipyrimidine photoproducts upon UVA irradiation of cells, purified genomic DNA and dA(20):dT(20) oligonucleotide duplex. We observed that the distribution of photoproducts, characterized by the sole formation of CPD and the absence of (6-4) photoproducts was similar in the three types of samples. The CPD involving two thymines represented 90% of the amount of photoproducts. Moreover, the yields of formation of the DNA lesions were similar in cells and isolated DNA. In addition, the effect of the wavelength of the incident photons was found to be the same in isolated DNA and cells. This set of data shows that UVA-induced cyclobutane pyrimidine dimers are formed via a direct photochemical mechanism, without mediation of a cellular photosensitiser. This is possible because the double-stranded structure increases the capacity of DNA bases to absorb UVA photons, as evidenced in the case of the oligomer dA(20):dT(20). These results emphasize the need to consider UVA in the carcinogenic effects of sunlight. An efficient photoprotection is needed that can only be complete by completely blocking incident photons, rather than by systemic approaches such as antioxidant supplementation.
DSM/INAC/SCIB UMR-E 3 CEA/UJF FRE CNRS 3200/Laboratoire Lésions des Acides Nucléiques, CEA-Grenoble, France.
Stéphane
S
Mouret
Coralie
C
Philippe
Jocelyne
J
Gracia-Chantegrel
Akos
A
Banyasz
Szilvia
S
Karpati
Dimitra
D
Markovitsi
Thierry
T
Douki
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003016:Clostridium perfringens / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000302:isolation & purification; D004249:DNA Damage / Q000528:radiation effects*; D004269:DNA, Bacterial / Q000737:chemistry / Q000302:isolation & purification; D016680:Genome, Bacterial / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D016982:Micrococcus luteus / Q000235:genetics; D010777:Photochemistry; D011740:Pyrimidine Dimers / Q000737:chemistry*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004269:DNA, Bacterial; D011740:Pyrimidine Dimers; D004247:DNA; C427203:calf thymus DNA