Photoinduced damage to cellular DNA: direct and photosensitized reactions.
The survey focuses on recent aspects of photochemical reactions to cellular DNA that are implicated through the predominant formation of mostly bipyrimidine photoproducts in deleterious effects of human exposure to sunlight. Recent developments in analytical methods have allowed accurate and quantitative measurements of the main DNA photoproducts in cells and human skin. Highly mutagenic CC and CT bipyrimidine photoproducts, including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are generated in low yields with respect to TT and TC photoproducts. Another striking finding deals with the formation of Dewar valence isomers, the third class of bipyrimidine photoproducts that is accounted for by UVA-mediated isomerization of initially UVB generated 6-4PPs. Cyclobutadithymine (T<>T) has been unambiguously shown to be involved in the genotoxicity of UVA radiation. Thus, T<>T is formed in UVA-irradiated cellular DNA according to a direct excitation mechanism with a higher efficiency than oxidatively generated DNA damage that arises mostly through the Type II photosensitization mechanism. C<>C and C<>T are repaired at rates intermediate between those of T<>T and 6-4TT. Evidence has been also provided for the occurrence of photosensitized reactions mediated by exogenous agents that act either in an independent way or through photodynamic effects.
Laboratoire Lésions des Acides Nucléiques, SCIB-UMR-E n°3, CEA/UJF, Institut Nanosciences et Cryogénie, CEA/Grenoble, Grenoble Cedex, France.
Jean
J
Cadet
Stéphane
S
Mouret
Jean-Luc
JL
Ravanat
Thierry
T
Douki
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D015603:Keratinocytes; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000494:pharmacology; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D004247:DNA