Altered electrophoretic migration of polycyclic aromatic hydrocarbon and styrene oxide adducts at adenine N-6 correlates with adduct-induced structural disorder

Site-specific bay region benzo[a]pyrene (7R,8S,9R,10S)-N-6-[10-(7,8,9,10-te trahydro-7,8,9-trihydroxybenzo[a] pyrenyl)] -2'-deoxyadenosyl, (7S,8R,9S,10 R)-N-6- [10-(7,8,9, 10-tetrahydro-7,8,9-trihydroxybenzo [a] pyrenyl)] -2'-d eoxyadenosyl, (7S,8R,9R,10S)-N-6-[10-(7,8,9, 10-tetrahydro-7,8,9-trihydroxy benzo[a] pyrenyl)] -2'-deoxyadenosyl, and (7R,8S,9S,10R)-N-6- [10-(7,8,9, 1 0-tetrahydro-7,8,9-trihydroxybenzo [a]pyrenyl)] -2'-deoxyadenosyl adducts, bay region benz[a]anthracene (1R,2S,3R,4S)-N-6-[1-(1,2,3,4-tetrahydro-2,3,4 -trihydroxybenz[a] anthracenyl)] -2'-deoxyadenosyl and( 1S,2R,3S,4R)-N-6- [ 1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz [a] anthracenyl)]-2'-deoxyadenos yl adducts, non-bay region benz[a]anthracenyl (8S,9R,10S,11R)-N-6-[11-(8,9, 10,11-tetrahydro-8,9,10-trihydroxybenz[a] anthracenyl)]-2'-deoxyadenosyl an d (8R,9S,10R,11S)-N-6-[11-(8,9,10,11-tetrahydro-8,9, 10-trihydroxybenz [a] anthracenyl)] -2'-deoxyadenosyl adducts, and the R- and S-adducts of styren e oxide were located in the ras61 oligodeoxynucleotide and examined with re spect to electrophoretic mobility. The results were compared to NMR structu ral data, and to site-specific mutagenesis data and in vitro DNA replicatio n assays for the same adducts. There was a correlation between adducts havi ng lower electrophoretic mobility and greater disorder at the adduct site a s monitored by NMR. The disorder combined with the lower electrophoretic mo bilities suggested that these adducts induced flexible hinge joints in the DNA rather than static bending. Usually, these were adenine N-6 adducts hav ing S-stereochemistry at the benzylic carbon. The results also revealed a p ossible role for the bay region ring in stabilizing adenyl N-6 benz[a]anthr acene adducts with respect to hinging at the adduct site. On the other hand , there was not a simple relationship between altered electrophoretic mobil ity and mutagenesis or DNA replication.