Genotoxicity of streptonigrin: a review

Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiot ic isolated from cultures of Streptomyces flocculus. This compound is a mem ber of a group of antitumor agents which possess the aminoquinone moiety an d 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 re duction with NADH, induces unscheduled DNA synthesis and DNA adducts and in hibits topoisomerase II. At the chromosome level, this antibiotic causes ch romosome 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 t he presence of NADH with production of oxygen-derived reactive species. Rec ent evidence strongly suggests that the clastogenic action of this compound is partially mediated by free radicals. The present review aims at summari zing past and current knowledge concerning the genotoxic effects of SN. (C) 2001 Elsevier Science B.V. All rights reserved.