STZ (Streptozotocin)

Streptozotocin directly methylates DNA and is highly genotoxic, producing DNA strand breaks, alkali-labile sites, unscheduled DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchanges, and cell death. Free radicals are involved in the production of DNA and chromosome damage by Streptozotocin. ^[1]

Streptozotocin is toxic to pancreatic beta cell. Exposed to 15 mM Streptozotocin for 1 hr followed by a 24 hrs recovery period induces apoptosis in murine pancreatic beta cell line, INS-1. Streptozotocin (30 mM) causes the cells to undergo necrosis (22%) as well as apoptosis (17%). ^[2]

Streptozotocin is often used to induce diabetes mellitus in experimental animals. Streptozotocin is selectively accumulated in pancreatic beta cells via the low-affinity GLUT 2 glucose transporter. Streptozotocin (60 mg/kg) injection for 4 month induces rapid degranulation of beta cells without necrosis, development of cataracts and accumulation of glycogen in the proximal convoluted tubules of the kidney. Streptozotocin (100 mg/kg) produces lesions in the exocrine cells of the pancreas, and persistence of small, possibly secretory, granules in the Golgi zone of beta cells in rats of ‘Streptozotocin diabetes’. ^[3]

Streptozotocin is found to be carcinogenic in rats, mice and hamster. A single administration of Streptozotocin is able to induce tumors in kidney, liver, lung, pancreas, uterine and liver tumors in hamster. Intraperitoneally injected with Streptozotocin (100-150 mg/kg) for normotensive Wistar Kyoto rats (WKY) for 12 months induces carcinogenesis with tumors incidence of 70% in liver, 20% in kidney and 10% in liver and kidney. ^[4]

• Cell lines

  INS-1 cells

• Concentrations

  15 mm

• Incubation Time

  1 h

• Method

  Cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period.

• Animal Models

  Male Holtzman rats

• Dosages

  50, 65, & 100 mg/kg

• Administration

  i.v.