Studies on the Chemical and Immunological Destruction of Insulin-Secreting Islet Cell Tumours

Summary

Chemical and immunological destruction of insulin-secreting islet cell tumours were evaluated in vivo and in vitro using the transplantable radiation-induced NBDH rat insulinoma and the derived clonal RINm5F cell line. Administration of a large amount of polyclonal insulin antibody did not affect the development of hypoglycaemia, tumour weights or the survival of insulinoma-bearing rats. Streptozotocin (100 mg/kg body weight) evoked a rapid and sustained decrease of insulin concentrations, accompanied by tumour regression and elevation of plasma glucose. Administration of alloxan (200 mg/kg) was without effect. In vitro, streptozotocin and alloxan exerted approximately equipotent time-dependent and concentration-dependent cytotoxic effects on cultured insulinoma cells as established by cell staining with trypan blue. The cytotoxic actions of both drugs were decreased by agents believed to scavenge free radicals or to act as inhibitors of poly (ADP-ribose) synthetase. Exposure of clonal RINm5F cells to the nitrosocompounds, N-methyl-N'-nitro-N-nitrosoguanidine and N-nitroso-N-methylurea, resulted in a particularly marked reduction in cell viability compared with streptozotocin.

Key Words

Alloxan - B-Cell Destruction - Hypoglycaemia - Insulinoma - Insulin Antibodies - Nitrosamides - Streptozotocin