GENOTOXIC EFFECTS OF STREPTOZOTOCIN ON MAMMALIAN CELLS: AN UPDATE

MARTHA S BIANCHI; SILVINA M RICHARD; ALEJANDRO BOLZAN

Advances in Medicine and Biology

NOVA SCIENCE PUBLISHERS INC.

Año: 2018; p. 129 - 161

Streptozotocin (Streptozocin, STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomycesachromogenes with broad spectrum antibiotic activity and antineoplastic properties. In particular, STZ is used alone or in combination with other drugs for the clinical treatment of pancreatic neuroendocrine carcinomas. Moreover, this compound is widely used to induce Type 1 diabetes mellitus in experimental animals through its toxic effects on pancreatic β-cells, and is also employed to induce Alzheimer?s disease in rodents. For the above reasons, the study of the toxic effects of STZ on mammalian cells is of great interest. In terms of STZ genotoxic effects, current evidence shows that this compound is a potent alkylating agent, inducing DNA strand breaks, covalent adducts, alkali-labile sites, unscheduled DNA synthesis and DNA synthesis inhibition. At the chromosome level, STZ induces chromosomal aberrations (including those ones involving telomeric sequences), micronuclei and sister chromatid exchanges. Moreover, recent evidence suggests that STZ induces long-term telomere instability in mammalian cells. In the present chapter, we will summarize our current knowledge regarding the toxic effects of STZ on mammalian DNA and chromosomes, putting emphasis on the most recent findings on this subject.