Bolzán A D, Bianchi M S
Laboratory of Cytogenetics and Mutagenesis, Instituto Multidisciplinario de Biología Celular (IMBICE), C.C. 403, 1900, La Plata, Argentina.
Mutat Res. 2001 Mar;488(1):25-37. doi: 10.1016/s1383-5742(00)00062-4.
Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiotic isolated from cultures of Streptomyces flocculus. This compound is a member of a group of antitumor agents which possess the aminoquinone moiety and that includes also mitomycin C, porfiromycin, actinomycin, rifamycin and geldanamycin. Because of the potential use of SN in clinical chemotherapy, the study of its genotoxicity has considerable practical significance.SN inhibits the synthesis of DNA and RNA, causes DNA strand breaks after reduction with NADH, induces unscheduled DNA synthesis and DNA adducts and inhibits topoisomerase II. At the chromosome level, this antibiotic causes chromosome damage and increases the frequency of sister-chromatid exchanges.SN cleaves DNA in cell-free systems by a mechanism that involves complexing with metal ions and autoxidation of the quinone moiety to semiquinone in the presence of NADH with production of oxygen-derived reactive species. Recent evidence strongly suggests that the clastogenic action of this compound is partially mediated by free radicals. The present review aims at summarizing past and current knowledge concerning the genotoxic effects of SN.
链黑菌素（SN，化学物质登记号：3930-19-6）是一种从絮凝链霉菌培养物中分离得到的氨基醌类抗肿瘤抗生素。该化合物是一类具有氨基醌部分的抗肿瘤药物成员，这一类药物还包括丝裂霉素C、卟吩霉素、放线菌素、利福霉素和格尔德霉素。由于链黑菌素在临床化疗中有潜在应用，对其遗传毒性的研究具有相当重要的实际意义。链黑菌素抑制DNA和RNA的合成，在经NADH还原后导致DNA链断裂，诱导DNA的非预定合成和DNA加合物形成，并抑制拓扑异构酶II。在染色体水平，这种抗生素会导致染色体损伤并增加姐妹染色单体交换频率。链黑菌素在无细胞系统中通过一种机制切割DNA，该机制涉及与金属离子络合以及在NADH存在下醌部分自氧化为半醌，同时产生氧衍生的活性物质。最近的证据有力地表明，该化合物的致断裂作用部分由自由基介导。本综述旨在总结过去和当前关于链黑菌素遗传毒性作用的知识。
