TOXI 51 |
| The polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (dB[a,l]P), is one of the most potent PAH carcinogens known in rodent model systems. Like other PAHs, it is metabolized in vivo to fjord region dB[a,l]P 11,12-diol 13,14-epoxides (DE) that bind to N2-dG and N6-dA in DNA. We studied the solution structure by NMR of a 14S(-)-trans-anti-dB[a,l]PDE-dG (G*) adduct opposite dC in an 11-mer duplex in a 5'-(...CG*C...)·(...GCG...) sequence context. We found conformational heterogeneity and disruption of base-pairing at G*:C and one to two 5'-flanking base pairs, depending on temperature, suggesting that the polycyclic aromatic DB[a,l]P residue is inserted into the helix 5' to the modified nucleoside. Removal of the C opposite G* in the complementary strand (5'-(...CG*C...)·(...G-G...) deletion duplex), changes the conformation to an intercalated one, as shown by two sharp, upfield shifted imino proton resonances. The susceptibilities of these two duplexes with different conformations to incision by nucleotide excision repair enzymes is being investigated to determine relationships between adduct structure and incision efficiency. Research supported by NIH grant CA 099194. |
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Poster Presentations and Awards
6:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 104, Poster
Sci-Mix
Division of Chemical Toxicology |