A-DNA accommodates adducts derived from diol epoxides of polycyclic aromatic hydrocarbons bound in a "side-stacking" mode.
The minor groove of undistorted A-DNA provides a good binding site for planar, hydrophobic moieties such as unmetabolized polycyclic aromatic hydrocarbons (PAHs), and the base pairs at the ends of short oligodeoxynucleotide helices. It also accommodates the chief adduct derived from the metabolically activated form of the carcinogen benzo[a]pyrene. B-DNA lacks such a site. Computerized models have been generated for the major (N2-guanine-linked) adducts formed at this site by both + and - enantiomers of anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) with poly(dG).poly(dC) in the A-DNA conformation. The BPDE adducts lie in the shallow, relatively hydrophobic minor groove of the A-DNA after empirical potential energy minimization using the program AMBER. We term this binding mode "side-stacking." The side-stacked + anti-BPDE may constitute the chief carcinogenic lesion derived from benzo[a]pyrene.
Andersen
R W
RW
Department of Chemistry, Boston University, Massachusetts 02215.
Whitlow
M D
MD
Teeter
M M
MM
Mohr
S C
SC
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000477:Alkylating Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D003198:Computer Simulation; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D004249:DNA Damage; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence
D000477:Alkylating Agents; D002273:Carcinogens; D004101:Dihydroxydihydrobenzopyrenes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA