Arylhydrazines are carcinogens that form C8-purine DNA adducts, however it is unclear how this leads to their carcinogenicity.  We have previously demonstrated that doubly modified oligonucleotides, that contain an arylhydrazine DNA adduct on each strand of the duplex, drive Z-DNA formation. Here, a hairpin-turn oligonucleotide has been designed to contain only one modification to compare with previous studies. The conformational effects were determined and quantitated by NMR and circular dichroism, respectively.   The B/Z-DNA equilibrium in oligonucleotide sequences with one or two modified bases are nearly identical indicating that the two modified purines exert their conformational effects independently.  This work suggests that one arylhydrazine DNA adduct can drive Z-DNA formation in oligonucleotide sequences near physiological conditions, which may provide a novel carcinogenic mechanism.  Future work will examine the interactions between Z prone modified oligonucleotides and Z-DNA binding proteins (Supported by a fellowship to BCT HEPC.dsr.09013 and NSF EPS-1003907).

Conformational analysis of the effect of a single C8-arylguanine mutation on the B/Z-DNA equilibrium:  An implication of arylhydrazine carcinogenesis

242nd National Meeting (2011)

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