Petrusek R L, Uhlenhopp E L, Duteau N, Hurley L H
J Biol Chem. 1982 Jun 10;257(11):6207-16.
Anthramycin, an antitumor antibiotic produced by Streptomyces refuineus, produces a well defined covalent adduct with DNA and lies within the narrow groove of DNA, attached through a thermal-labile covalent animal linkage to the exocyclic amino group of guanine, without detectable distortion of the helix (Petrusek, R. L., Anderson, G. L., Garner, T. F., Fannin, Q. L., Kaplan, D. J. Zimmer, S. G., and Hurley, L. H. (1981) Biochemistry 20, 1111-1119). This paper described results in which the biological consequences of DNA damage and repair by repair-proficient and a repair-deficient xeroderma pigmentosum (XP 12RO) cell line are presented. Anthramycin has been shown to produce excision-dependent single and double strand breaks in DNA, both of which appear to persist many hours after removal of the drug from the media. The lower ability of the xeroderma pigmentosum cell line to remove ability of the xeroderma pigmentosum cell line to remove anthramycin lesions from DNA is correlated with a decreased cell survival. The biological consequences of DNA damage (genetic effects, DNA strand breakage, and cytotoxicity) are discussed with respect to the defined structure and stability of the anthramycin-deoxyguanosine adduct.
安丝菌素是由精致链霉菌产生的一种抗肿瘤抗生素，它与DNA形成一种明确的共价加合物，并位于DNA的窄沟内，通过一个热不稳定的共价连接与鸟嘌呤的环外氨基相连，而不会使螺旋结构发生可检测到的扭曲（彼得鲁塞克，R. L.，安德森，G. L.，加纳，T. F.，范宁，Q. L.，卡普兰，D. J.，齐默尔，S. G.，以及赫尔利，L. H.（1981年）《生物化学》20，1111 - 1119）。本文描述了相关结果，其中呈现了修复能力正常和修复缺陷的着色性干皮病（XP 12RO）细胞系对DNA损伤和修复的生物学后果。已证明安丝菌素会在DNA中产生依赖切除的单链和双链断裂，在从培养基中去除该药物后，这两种断裂似乎会持续存在数小时。着色性干皮病细胞系从DNA中去除安丝菌素损伤的能力较低，这与细胞存活率降低相关。针对安丝菌素 - 脱氧鸟苷加合物的明确结构和稳定性，讨论了DNA损伤的生物学后果（遗传效应、DNA链断裂和细胞毒性）。
