Immunohistochemical localization of copper-zing and manganese superoxide dismutases in diisopropanolnitrosamine-induced rat thyroid lesions.

The immunohistochemical localization of both copper-zinc (Cu, Zn) and manganese (Mn) superoxide dismutases (SODs) in diisopropanolnitrosamine (DIPN) induced rat thyroid lesions was examined.In normal thyroid tissue, Cu, Zn-SOD was homogeneously demonstrated in both the nucleus and cytoplasm of the follicular epithelium, whereas Mn-SOD was present in the cytoplasm in a granular pattern.The lesions of diffuse hyperplasia, which are regarded as early changes induced by DIPN administration, showed almost the same pattern, but in places a partial decrease in staining intensity was observed compared to thyroid tissue of the control animals and DIPN-treated animals with no remarkable lesions. In both benign (types 1 and 2) and malignant (type 3) lesions, the overall staining intensity of Cu, Zn-SOD and Mn-SOD was decreased. However, in some malignant lesions (type 3), a focal increase in staining of SODs was observed. In foci of degeneration and necrosis, relatively strong expression of Mn-SOD was seen in the thyroid follicular epithelium as well as in mesenchymal cells. In addition, an inverse correlation was noted between Cu, Zn-SOD and Mn-SOD localization in the lesions of diffuse hyperplasia and benign and malignant nodules.These findings suggest a possible correlation between alterations of SOD activities and thyroid tumorigenesis, and the existence of regulatory mechanisms for SOD expression.