Genotoxicity of streptonigrin: a review.
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.
Laboratory of Cytogenetics and Mutagenesis, Instituto Multidisciplinario de Biología Celular (IMBICE), C.C. 403, 1900, La Plata, Argentina. adbolzan@netverk.com.ar
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Bianchi
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D019457:Chromosome Breakage; D002875:Chromosomes / Q000187:drug effects*; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D013308:Streptonigrin / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D005609:Free Radicals; D009153:Mutagens; D019384:Nucleic Acid Synthesis Inhibitors; D013308:Streptonigrin; D004247:DNA