Induction of Orthotopic Rat Adrenomedullary Neoplasia by Intraadrenal Pheochromocytoma Cell Transplantation

Abstract

We aimed to establish a technically feasible, easily reproducible model of orthotopic adrenomedullary neoplasia. Male rats received adrenal injection of rat pheochromocytoma cells infected with the Escherichia coli gene for beta-galactosidase (lac Z). Each of 10 animals was perfused 7 or 24 days after tumor cell injection; 5 animals of each group were injected with cyclosporin. Animals without tumor cell injection served as controls. Tumor cells were identified and characterized in frozen sections by histochemical and immunohistochemical methods. Immunosuppressed animals had enlarged adrenals 7 days after tumor cell injection. In the rats without immunosuppression the adrenals seemed unaltered despite microscopic demonstration of tumor cells. After 24 days tumors had developed in all animals, weighing 50 times more than normal adrenals in animals with immunosuppression, and 9 times more in animals without immunosuppression. Intraadrenal catecholaminergic tumor cells could be identified by beta-galactosidase expression. No animal showed systemic spread. Generation of adrenomedullary neoplasia by intraadrenal pheochromocytoma cell transplantation is easily reproducible and technically feasible. This model allows simultaneous study of neoplastic and normal adrenal tissues (e.g., regarding their response to drugs intended for diagnostic and therapeutic purposes). The decreased tumor growth in animals without immunosuppression is presumably due to the high number of intraadrenal immunocompetent cells.