Diethylnitrosamine-lnduced Changes in Mouse Liver Morphology and Function 1

Abstract

Summary

Long-term administration of DEN to adult Swiss mice for periods of up to 24 weeks resulted in intense bile duct proliferation, formation of hepatic nodules, some of which appeared to be hyperplastic, and foci of lymphocytic infiltration. No hep-atocellular carcinomas or well-defined hepa-tomas were found in these DEN-treated mice. The only tumors observed were one hemangioma, and in 2 sections, tissue suggestive of cholangiocarcinoma. The significant increases in hexobarbital sleeping times and the striking resistance to the hepa-totoxic effects of CC1₄ in DEN-treated mice indicated that long-term exposure to DEN resulted in a progressive inhibition of liver DMES activity. Phenobarbital administration concurrent with DEN prevented the decreases in hexobarbital sleeping times but did not alter the morphologic changes in the liver produced by DEN, at least at the light microscopic level.