The efffect of glucocorticoid to oncogenesis of chemically induced pancreatic islet cell tumors was studied. This work was carried out on Sprague-Dawley rats received with two different tumorigenic agents, respectively. In the first series,5-weeks-old male rats started to be injected intravenously by 10 mg/kg or 20 mg/kg of 6-Diethylaminomethyl-4-hydroxyaminoquinoline-1-oxide (6-DEAM-4-HAQO) once a week in 8 weeks according to Hayashi's method. In the second one,70-days-old male rats were injected intravenously by 50 mg/kg of Streptozotocin (STZ), preceded and followed by an intraperitoneal injection of Nicotinamide, as well as the method of Rakieten et al. As the glucocorticoid administration, Fluocortolone (FC) was injected continuously, singly or combined with these chemical agents. FC, a kind of hydrocortisone derivatives donated by Shering Co., was injected subcutaneously, either 0.4-0.6ing/kg daily and later 3 times a week in the ages from 115 days to 360 days in the first experiment or 0.8 mg/kg twice a week in the ages from 150 days to 230 days in the second one. The survivals more than 500 days in the first series and 490 days in the second one were counted as the effective cases for these experiments. The induction rate of pancreatic islet cell tumors was as follows: 6-DEAM-4-HAQO 10 mg/kg alone; 25%, its combined with FC; 14%,6-DEAM-4-HAQO 20 mg/kg alone; 40%, its combind with FC; 80%, STZ alone; 25%, and its combined with FC; 90%. No pancreatic islet cell tumor was present in the untreated control and FC alone treated groups in both experimental serieses. The results revealed that a hyperglucocorticoid state enhanced the tumorigenesis of pancreatic islet cells induced with the chemical agents. The elevation of serum insulin was noted only in two rats bearing big islet cell tumors, 'but the histochemical or ultrastructural observations indicated that all of induced pancreatic islet cell tumors were diagnosed as B cell adenoma. No any adenomas of A cell or other cells of the pancreatic islets could be developed, although small clusters of them were occasionally detectable in the pancreatic tissues. In the glucocorticoid-treated rats, especially the carcinogen combined animals, B cell hyperplasia and nesidioblastic changes were prominently found. This observation suggests that glucocorticoid may increase the precursor cells of pancreatic islet cell tumor and also enhance the differentiation of these transformed cells to the pancreatic islet B cell.
