STUDIES ON THE TISSUE-DISPOSITION AND FATE OF [14C]STREPTOZOTOCIN WITH SPECIAL REFERENCE TO THE PANCREATIC ISLETS

Abstract

The tissue-disposition and fate of [14C]streptozotocin labelled in the methyl-group of the N-nitrosomethylurea side-chain, were studied in mice. Whole-body autoradiography, quantified by densitometric measurements, showed that the pancreatic islets had a high capacity to accumulate radioactivity after the injection of [14C]streptozotocin. Microautoradiography of the pancreas showed that centrally located cells were labelled while peripherally located cells contained a low labelling, indicating a selective labelling of the .beta.-cells. A high radioactivity was present in the liver and the renal cortex at most survival intervals. About 17% of the radioactivity was exhaled as 14CO2 during 6 h, which shows that the methyl group of the N-nitrosomethylurea side-chain is split off. Radioactivity was shown to be incorporated in the acid-insoluble precipitate of the pancreatic islets, the liver, the kidney, and the exocrine pancreas. This may, to a varying extent, be due both to alkylating reactions and to incorporation of radioactivity in the macromolecules of the tissues via normal metabolic pathways. About 44% of the radioactivity was excreted as unchanged [14C]streptozotocin in the urine during 24 h, while about 1% of the radioactivity was found in the feces. Whole-body autoradiography of [14C]streptozotocin in 2 Chinese hamsters and 1 rat also showed a high accumulation of radioactivity in the pancreatic islets in these species.