We have investigated the ability of the diabetogenic drug streptozotocin (SZ) to induce DNA repair synthesis following DNA lesions in the cells of the islets of Langerhans of mice. Following intravenous injection of SZ, the pancreatic islets were isolated and incubated with tritiated thymidine. The incorporation of the isotope into cells performing DNA repair synthesis was analyzed using quantitative autoradiography. SZ induced an acute hyperglycemia in the mice together with a significant DNA repair synthesis (an increased tritiated thymidine incorporation) in the islet cells. In similar experiments performed with alloxan, the islet cells degenerated rapidly preventing the detection of DNA repair synthesis. The results support the view that SZ acts on the B cell by causing DNA damage followed by DNA repair synthesis. However, the rapid islet cell degeneration observed following alloxan administration suggests that this B cytotoxin has a different primary mechanism of action, from that of SZ.
Animals Blood Glucose