Goldberg I H
Free Radic Biol Med. 1987;3(1):41-54. doi: 10.1016/0891-5849(87)90038-4.
The molecular mechanisms by which the antitumor protein antibiotic, neocarzinostatin, interacts with DNA and causes DNA sugar damage is discussed. Physical binding of the nonprotein chromophore of neocarzinostatin to DNA, involving an intercalative process and dependent on the microheterogeneity of DNA structure, is followed by thiol activation of the drug to a probable radical species. The latter attacks the deoxyribose, especially at thymidylate residues, by abstracting a hydrogen atom from C-5' to generate a carbon-centered radical on the DNA. This nascent form of DNA damage either reacts with dioxygen to form a peroxyl radical derivative, which eventuates in a strand break with a nucleoside 5'-aldehyde at the 5'-end or reacts with the bound drug to form a novel drug-deoxyribose covalent adduct. Nitroaromatic radiation sensitizers can substitute for dioxygen, but the DNA damage products are different. Similarities between the various biological effects of neocarzinostatin and ionizing radiation are reviewed.
本文讨论了抗肿瘤蛋白抗生素新制癌菌素与DNA相互作用并导致DNA糖损伤的分子机制。新制癌菌素的非蛋白发色团与DNA的物理结合涉及嵌入过程，并依赖于DNA结构的微异质性，随后药物被硫醇激活为可能的自由基物种。后者通过从C-5'提取氢原子攻击脱氧核糖，特别是在胸苷酸残基处，从而在DNA上产生以碳为中心的自由基。这种新生形式的DNA损伤要么与双氧反应形成过氧自由基衍生物，最终导致在5'-末端形成带有核苷5'-醛的链断裂，要么与结合的药物反应形成新型药物-脱氧核糖共价加合物。硝基芳香族辐射增敏剂可以替代双氧，但DNA损伤产物不同。本文还综述了新制癌菌素与电离辐射各种生物学效应之间的相似性。
