The effect of N-nitroso-2-methoxy-2,6-dimethylmorpholine on endocrine and exocrine pancreas of Syrian hamsters

Abstract

N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM), a cyclic derivative of the proposed proximate pancreatic carcinogen N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), is shown to have an almost selective cytotoxic effect on pancreatic beta-cells when a single high dose is given to Syrian hamsters. Hence in this aspect its effect is comparable to that of streptozotocin, which has a glucose moiety similar to the MeNDMM structure. However, contrary to the effect of streptozotocin, low single (subdiabetogenic) doses of MeNDMM led to the development of pancreatic ductular and mixed ductular-insular neoplasms; only 1 animal also had islet cell adenoma. It therefore seems that MeNDMM possesses an affinity for both endocrine and exocrine pancreatic tissue. Other target tissues of MeNDMM were the forestomach, intra- and extrahepatic bile ducts, liver, kidneys and vagina. The tumors of these organs appeared in various incidences, partially in relation to dose and/or survival time. The possible mechanisms of the MeNDMM effect upon the endocrine and the exocrine pancreas is discussed.