Hyperglycemia and hepatic tumors in ICR mice neonatally injected with streptozotocin

Repeated, low-dose administration of streptozotocin (STZ) is widely used to induce insulin-dependent diabetes mellitus in mice. The authors adapted this method using neonatal mice and determined the long-term effects of STZ injection in the mice. After receiving intraperitoneal injections of STZ at postnatal day 3 (P3), P4 and P8, male and female mice were hyperglycemic by week 4. A clear sex difference was found, with blood glucose levels in STZ-treated males remaining higher than those in STZ-treated females until week 23. Whereas STZ-treated males remained hyperglycemic until week 23, STZ-treated females did not have significantly higher glucose levels than control mice after week 18. Additionally, STZ-treated mice had neoplastic lesions in their livers by week 4, with a progression in the severity of these lesions until week 24. The results confirm that, in addition to pancreatic beta cell toxicity, STZ has an oncogenic effect on the liver when administered to neonates.