Alkylation of anionic DNA bases by styrene 7,8-oxide

Styrene 7,8-oxide (SO), a reactive epoxide that has been classified as a pr obable human carcinogen, was allowed to react under alkaline conditions wit h 21-deoxyguanosine and thymidine monophosphates as well as with the dinucl eotide dGpdT. The reaction products were separated by high-performance liqu id chromatography and were characterised by UV and electrospray mass spectr oscopy, the latter showing the ability to differentiate the isomerism of th e hydroxyphenylethyl moiety of the adduct. The main alkylation products of the deoxyguanosine monophosphates at high pH were those reacted at the 1- ( through the beta-carbon of the epoxide), N-2- (alpha-carbon) and 7-position s (beta- and alpha-carbons) of guanine followed by alkylation of the phosph ate group. The formation of a novel diastereomeric pair of N-2-guanine addu cts connected to the beta-carbon of SO was identified and characterised. Fu rthermore, two different geometrical isomers of 1-guanine were detected. Fo r thymidine nucleotide, base alkylation under neutral conditions was almost negligible, but at pH 10.5, alkylation at the 3-position was very prominen t. The same base-adducts and the pH-effects were observed in the case of dG pdT alkylation. However, no phosphate alkylation was detected in the case o f the dinucleotide.