Slor H, Bynum G D, Lee C H, Mizusawa H, Kakefuda T
Jpn J Cancer Res. 1985 Jun;76(6):488-95.
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.
评估了DNA的螺旋构象对抗体与DNA - 致癌物加合物结合的影响。通过使用热变性、有机溶剂和阳离子改变DNA螺旋的缠绕角度，来调节抗体与经（+）-反式-7β，8α-二羟基-9α，10α-环氧-7,8,9,10-四氢苯并[a]芘（BPDE）处理后在DNA中产生的加合物的结合效率。DNA螺旋的解旋和完全变性使抗体与DNA - BPDE加合物的结合效率比其与未受干扰的双螺旋DNA中的BPDE加合物的结合效率提高了4至8倍。抗体结合效率与由二甲基亚砜、乙二醇或甘油诱导的双螺旋解旋程度成正比。相反，单价阳离子（Na +、K +、Rb +、Li +、Cs +和NH4 +）使双螺旋缠绕，而二价阳离子（Mg2 +、Ca2 +、Mn2 +、Sn2 +和Ba2 +）更有效地使双螺旋缠绕，这会降低抗体与DNA - BPDE加合物的结合。我们认为，BPDE加合物在螺旋沟内的分子取向调节了加合物与抗体分子结合的可及性。通过螺旋的打开和/或解旋，部分“埋藏”在沟内的BPDE加合物（或其免疫原性位点）可能会不同程度地暴露于抗体结合。相反，螺旋的缠绕会使BPDE加合物免受抗体识别和结合。
