【作者】 赵丽娇； 钟儒刚；

【Author】 ZHAO Li-Jiao,ZHONG Ru-Gang College of Life Science and Bioengineering,Beijing University of Technology,Beijing,100022

【机构】 北京工业大学生命科学与生物工程学院；

【摘要】 N-亚硝基化合物(NNCs)是一类重要的致癌物质,其在体内经过代谢活化或分解后能够形成活泼亲电试剂与DNA碱基发生烷化反应,导致DNA损伤而最终诱发癌症。亚硝胺是其中一类重要的致癌剂,它们在细胞色素P450作用下代谢生成α,β-羟基亚硝胺导致难以修复的DNA横向交联。在大多数NNCs被认为是致癌物的同时,一些亚硝基脲类化合物却表现出了抗癌活性,比如氯乙基亚硝基脲(CENUs)就是目前临床上一类重要的抗癌药物。CENUs是一类双官能团烷化剂,它能够在生理条件下分解生成氯乙基正离子等活泼亲电试剂,导致DNA横向交联进而抑制癌细胞DNA的复制。然而,临床应用发现CENUs在抗癌的同时还能够导致病人的二次肿瘤,而且其致癌副作用也与导致DNA交联有关。因此不论NNCs的致癌作用还是抗癌作用,其中导致DNA横向交联都是关键步骤,但是,交联的机理是否存在差异目前尚不清楚。更多还原

【Abstract】 N-nitroso compounds(NNCs) are an important family of carcinogens.They undergo metabolism or decomposition to generate active electrophiles,which lead to DNA damage by alkylating bases and result in cancer finally.Nitrosamines are one significant kind of NNCs.They are metabolized toα,β-hydroxyl nitrosamines by cytochrome P450.The metabolites are able to induce DNA interstrand crosslinks(ICLs),which is difficult to be repaired.While most NNCs are considered as carcinogens,some nitrosoureas exhibit antitumor activities.For example, chloroethylnitrosoureas(CENUs) are an important group of agents used in the clinical treatment of cancer.CENUs are bifunctional alkylating agents and decompose under physiological conditions to generate chloroethyl cations.They can prevent DNA replication of cancer cells by inducing DNA ICLs.However,clinical application indicated that CENUs could cause the second cancer of patients,which were also related to the induction of DNA ICLs.Therefore,ICLs is supposed to be the key step in both carcinogenesis and anticancer effect of NNCs.But,it is not clear that whether there is difference between the mechanism of ICLs by nitrosamines and nitrosoureas.更多还原