Individual determination of the yield of the main UV-induced dimeric pyrimidine photoproducts in DNA suggests a high mutagenicity of CC photolesions.
Bipyrimidine photoproducts induced in DNA by UVB radiation include cyclobutane dimers, (6-4) photoproducts, and their related Dewar valence isomers. Even though these lesions have been extensively studied, their rate of formation within DNA is still not known for each possible bipyrimidine site (TT, TC, CT, and CC). Using a method based on the coupling of liquid chromatography to mass spectrometry, we determined the distribution of the 12 possible bipyrimidine photoproducts within isolated and cellular DNA. TT and TC were found to be the most photoreactive sequences, whereas lower amounts of damage were produced at CT and CC sites. In addition to this quantitative aspect, sequence effects were observed on the relative yield of (6-4) adducts with respect to cyclobutane pyrimidine dimers. Another interesting result is the lack of formation of Dewar valence isomers in detectable amounts within the DNA of cells exposed to low doses of UVB radiation. The photoproduct distribution obtained does not fully correlate with the UV mutation spectrum. A major striking observation deals with the low yield of cytosine-cytosine photoproducts which are likely to be associated with the UV-specific CC to TT tandem mutation.
Douki
T
T
Département de Recherche Fondamentale sur la Matière Condensée/Service de Chimie Inorganique et Biologique UMR 5046/Laboratoire des Lésions des Acides Nucléiques, CEA/Grenoble, 17, avenue des Martyrs, F-38054 Grenoble Cedex 9, France.
Cadet
J
J
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D015226:Dinucleoside Phosphates / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007536:Isomerism; D008027:Light; D013058:Mass Spectrometry; D009000:Monocytes / Q000378:metabolism / Q000528:radiation effects; D016296:Mutagenesis / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects*; D013941:Thymine / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D015226:Dinucleoside Phosphates; D011740:Pyrimidine Dimers; D003596:Cytosine; D004247:DNA; D013941:Thymine