Toxicologic Evaluation of Streptozotocin (NSC 85998) in Mice, Dogs and Monkeys

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Abstract
Streptozotocin (SZN), an N-methylnitrosourea antibiotic, is the chemotherapeutic agent used for the treatment of malignant insulinoma in man. Single i.v. doses in CDF1 mice, and single and 5 daily i.v. treatment schedules in beagle dogs and rhesus monkeys were used to evaluate the toxicity of SZN. The major target organs in the 3 spp. were liver, kidney, lymphoid tissue and pancreatic islet .beta.-cells. Moderate bone marrow depression and gastrointestinal toxicity were observed in the large animal species after lethal doses. Monkeys were less sensitive than the dog to the hepatotoxic effects of SZN and clinical signs of liver dysfunction were more severe in dogs after multiple doses. Microscopic lesions in the renal proximal convoluted tubules were present in the 3 spp.; these lesions appeared to be irreversible for dogs. The toxic effect on the endocrine pancreas was manifest by hyperglycemia, glucosuria, islet atrophy and .beta.-cell degranulation. Multiple dose regimens were less toxic than single doses in dogs and monkeys in terms of the total dose received.