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1979年,戴乾圜提出的化学致癌机理的双区理论发现:环境致癌剂均代谢成特定的双官能烷化剂,并通过诱发DNA互补碱基交联而启动癌变.戴乾圜当时解释互补碱基交联启动细胞癌变的根源时指出:DNA即基因的突变主要都是由缺乏互补模板的交联的互补碱对所诱发(易于依靠互补模板修复的单个碱基损伤只有远为次要的作用),而突变的基因借逆转录机制经历潜伏期而引起细胞的深度突变即奇异染色体的产生和细胞的最后癌变.致癌剂的致突变谱、癌细胞中奇异染色体的结构、逆转录机制在正常细胞中的广泛存在和致癌剂均能诱发DNA股间交联等,都从实验上证明了双区理论所揭示的上述致癌过程的分子机理.传统的抗癌剂都是基因毒性的,即抗癌剂均具有强力的致癌、致畸胎、致不育和致突变的潜力.作者首次将致癌剂的抗癌药效和基因毒性的差别,定义为抗癌剂的选择性.作者发现可以突破抗癌剂的随机筛选和偶然发现的方式,借双区理论按照理论预想设计高选择性抗癌剂.实践证明:抗癌烷化剂本身或代谢后都是双官能烷化剂.戴乾圜将双官能抗癌烷化剂在DNA碱基之间的交联,划分为易于修复的股内或股间非互补碱基间的、不具致癌性的良性交联,和难于修复的互补碱基间的、表现致癌性的恶性交联.因此双区理论设计高选择性抗癌剂的理论观点认为:应力求
In 1979, Dai Qianli proposed a two-zone theory of mechanism of chemical carcinogenesis found that: environmental carcinogens are metabolized into a specific bifunctional alkylating agent, and by inducing DNA base complementation and start of cancer. Baseline crosslinking triggers the root cause of cellular carcinogenesis and states that mutations in DNA, ie genes, are predominantly induced by a pair of complementary bases complementary to a complementary template (only a single base injury prone to relying on complementary template repair is far less important , While the mutated genes undergo the latent period through the reverse transcription mechanism to cause the deep mutation of the cells, namely the production of the singular chromosomes and the final carcinogenesis of the cells.The mutagenicity spectrum of the carcinogens, the structure of the singular chromosomes in the cancer cells, the mechanism of the reverse transcription in the normal Widely existing in cells and carcinogens can induce DNA inter-strand cross-linking, etc., have experimentally proved the dual-region theory reveals the molecular mechanism of the above carcinogenic process.Traditional anticancer agents are genotoxic, that is, anti Cancer agents have a strong carcinogenic, teratogenic, infertility and mutagenic potential for the first time the author of the carcinogen anticancer efficacy and genotoxic differences, defined as the selection of anti-cancer agent The authors found that breakthroughs in anti-cancer agents can be randomly selected and occasionally discovered by the way, by dual-zone theory according to the theoretical design of highly selective anti-cancer agent.Practice has proved that: anticancer alkylating agent itself or after the metabolism of bifunctional alkanes Agent.Dai Gan 圜 the bifunctional anti-cancer alkylating agent in the DNA between the base of the cross-linked, divided into easy to repair intra-strands or non-inter-strata non-cancerous benign cross-linking, and Difficult to repair the complementary bases, the performance of malignant cross-linking .Therefore, the theory of dual-area design of highly selective anticancer agents that: stress