Department of Biochemistry, J.N. Medical College, Aligarh Muslim University, Aligarh, India.
IUBMB Life. 2012 Apr;64(4):340-5. doi: 10.1002/iub.1008. Epub 2012 Feb 29.
4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed.
4-氨基联苯是一种已知的致癌物质，有许多环境来源，如香烟烟雾、工业废物等。它可以代谢形成一种强诱变剂，N-羟基-N-乙酰-4-氨基联苯（N-OH-AABP），进一步加工形成亲电的亚硝酰离子，与 DNA 形成共价加合物，从而产生遗传毒性作用。虽然 N-OH-AABP 的致突变性已有充分报道，但尚未进行广泛研究来评估 N-OH-AABP 修饰的 DNA 的免疫原性。在这项研究中，用人胎盘 DNA 修饰 N-OH-AABP，通过紫外光谱和核酸酶 S1 消化来评估 DNA 分子的结构扰动。将天然和 N-OH-AABP 修饰的 DNA 用作抗原免疫雌性兔子。结果发现修饰的 DNA 具有高度的免疫原性，能引起高滴度的免疫原特异性抗体，而天然形式几乎没有免疫原性。诱导的抗体在识别各种核酸构象和 DNA 碱基方面表现出广泛的异质性。我们还在用 N-OH-AABP-DNA 免疫的兔子的肾小球基底膜中检测到免疫复合物的沉积。讨论了 N-OH-AABP-DNA 在诱导癌症患者抗体中的可能作用及其相关后果。
