Enhanced tumorigenicity of insulinoma by X-irradiation of the gastric regions in Sprague–Dawley male rats.

Abstract Background and Aims: There has been no suitable animal model for human insulinoma because incidence of pancreatic tumours induced by whole-body irradiation or chemicals has been very low. The purpose of this study was to establish an experimental model with a high incidence of insulinoma. The induction of islet cell tumour by X-irradiation was investigated. Methods: Forty Sprague–Dawley male rats were used in this study. Twenty-eight rats were irradiated with two 10-Gy doses to the gastric region at a 3-day interval, and 12 rats not subjected to X-irradiation served as a control group. The rats were killed 16 months after the first irradiation. Expression of insulin mRNA and protein was examined by northern blot analysis and immunohistochemistry, respectively. Rat serum insulin and glucose levels were measured using enzyme-linked immunosorbent assay. Results: Tumour incidence was 89.3% (25/28) in X-ray group and 8.3% (1/12) in the control group (P < 0.05). Pancreatic tumours, which appeared in all 25 rats with tumours, showed the highest incidence of all neoplasms detected. Tumour cells showed strong immunoreactivity for insulin in 20 of 25 pancreatic tumours (80%). Expression of insulin mRNA was confirmed by northern blot analysis. Furthermore, rats with pancreatic tumours had lower serum glucose levels and higher insulin levels than the control rats. Conclusion: X-irradiated SD rats may be considered a suitable model for insulinoma because of their high tumorigenicity. [ABSTRACT FROM AUTHOR]