Effect of DNA conformation on the binding of antibodies to benzo[a]pyrene diol-epoxide DNA adducts.
The effect of the helical conformation of DNA on the binding of antibodies to DNA-carcinogen adducts was evaluated. The efficiency of antibody binding to adducts produced in DNA by treatment with (+)-trans-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was modulated by varying the winding angle of the DNA helix using heat denaturation, organic solvents, and cations. Unwinding and complete denaturation of the DNA helix increased the binding efficiency of anti-bodies to DNA-BPDE adducts 4- to 8-fold over that to BPDE adducts in the unperturbed double helical DNA. The antibody binding efficiency increased in proportion to the degree of unwinding of the double helix induced by dimethylsulfoxide, ethylene glycol, or glycerol. Conversely, winding of the double helix with monovalent cations (Na+, K+, Rb+, Li+, Cs+ and NH4+) and more effectively with divalent cations (Mg2+, Ca2+, Mn2+, Sn2+ and Ba2+) decreased antibody binding to DNA-BPDE adducts. We suggest that the molecular orientation of BPDE adducts within helical grooves modulates adduct accessibility for binding with antibody molecules. By the opening and/or unwinding of the helix, BPDE adducts (or their immunogenic sites) partially "buried" within the grooves may be exposed to varying degrees for antibody binding. Conversely, winding of the helix shielded the BPDE adducts from antibody recognition and binding.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000906:Antibodies / Q000378:metabolism; D001580:Benzopyrenes / Q000276:immunology*; D004247:DNA / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation
D000906:Antibodies; D001580:Benzopyrenes; D004277:DNA, Single-Stranded; D005026:Ethylene Glycols; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D019855:Ethylene Glycol; D005990:Glycerol; D004121:Dimethyl Sulfoxide