Genotoxic effects of Streptozotocin

ALEJANDRO D. BOLZAN

Streptozotocin: Uses, Mechanism of Action and Side Effects

Nova Science Publishers

Año: 2014; p. 99 - 120

Streptozotocin (Streptozocin, STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes with broad spectrum antibiotic activity and antineoplastic properties. This compound is often used to induce diabetes mellitus in experimental animals through its toxic effects on pancreatic B-cells. STZ is a potent alkylating agent known to directly methylate DNA, thus inducing DNA damage by alkylation of specific sites on DNA bases. DNA lesions produced by STZ includes double and single-strand breaks, covalent adducts and alkali-labile sites. Moreover, STZ induces unscheduled DNA synthesis and DNA synthesis inhibition. Severe DNA damage by STZ results in cell death by apoptosis or necrosis. The DNA strand breaks resulting from the alkylating action of STZ can lead to chromosomal rearrangements. Accordingly, STZ tests positive in the chromosomal aberrations, micronuclei and sister chromatid exchanges assays. In addition, this antibiotic was found to be mutagenic in bacterial assays and eukaryotic cells and is also carcinogenic: a single administration of STZ induces tumors in rat kidney, liver, and pancreas. Since STZ is used as an antineoplastic agent for the treatment of pancreatic neuroendocrine carcinomas, the study of its genotoxicity is of great importance to understand the genomic instability associated with chemotherapy regimens involving administration of this antibiotic. Therefore, the purpose of this chapter is to summarize the current knowledge regarding the genotoxic effects of STZ.