Development and applications of an animal model for human tumor xenografts

Wistar rats treated with cyclophosphamide (4x 10 mg/kg), total lymphoid irradiation (9.0 Gy; dose rate 0.60 Gy/min) and cyclosporin A (15 mg/kg, daily, orally) developed a state of immune suppression permitting the growth of human tumor xenografts. Immunosuppression was monitored by lymphocyte counts, serum IgG determination. PHA and Con A lymphocyte-responses, proportion of B cells and histopathological studies of the lymphoid organs. The lymphocyte counts, IgG levels, PHA and Con A stimulation values remained severely depressed, during the period of cyclosporin A administration. Repopulation of the paracortical areas of the lymph nodes and the peri-arteriolar sheaths of the spleen did not occur, neither the reconstruction of the germinal centers in these organs. The thymus underwent severe atrophy. Seven of eight different types of human tumors were successfully xenografted in the immunomodified rat. The xenografted tumors maintained their original morphologic features and the mitotic rate did not change during subsequent transplantations.