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 cyclobut ane dimers, (6-4) photoproducts, and their related Dewar valence isomers. E ven though these lesions have been extensively studied, their rate of forma tion 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 chromatogr aphy to mass spectrometry, we determined the distribution of the 12 possibl e bipyrimidine photoproducts within isolated and cellular DNA. TT and TC we re found to be the most photoreactive sequences, whereas lower amounts of d amage were produced at CT and CC sites. In addition to this quantitative as pect, 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 wit hin the DNA of cells exposed to low doses of UVB radiation. The photoproduc t distribution obtained does not fully correlate with the UV mutation spect rum. A major striking observation deals with the low yield of cytosine-cyto sine photoproducts which are likely to be associated with the UV-specific C C to TT tandem mutation.