Venoocclusive disease of the liver and phlebectatic peliosis in the golden hamster exposed to dimethylnitrosamine.
The liver of Syrian hamsters was studied after exposure to dimethylnitrosamine (DMN) in drinking water for, respectively, 8, 12 and 16 weeks. One additional group of animals was offered DMN for 8 weeks, but maintained for further 8 weeks after removal of the compound. The changes consisted of a narrowing portal venopathy, probably arising, initially, from toxic pylephlebitis, being followed by widespread subendothelial prolapse of hepatocytes encroaching upon the lumen of terminal hepatic veins, which generally were free of inflammatory fibrosing lesions. The venous lesions were unrelated to malignant processes in the biliary duct system, which occurred after 16 weeks. Dilatation of sinusoids and small venules was associated with the presence of prolapsed hepatocytes around their openings into involved larger veins. At the end of 12 and 16 weeks of continuous ingestion of DMN, but also where the agent was withdrawn already at 8 weeks, phlebectasis and transitional stages in the formation of teleangiactatic type of peliosis were demonstrated, probably resulting from progressively impeded blood flow due to partial occlusion by prolapsed hepatocytes in terminal veins. The mechanism enabling hepatocytes to penetrate the venous wall was not clarified. There was no indication of invasive malignancy. Hepatocyte prolapse appeared more likely to result from some unknown mechanism of benign infiltration, promoted by regenerative stimulation. This may have been initiated by mild persistent ischemia due to the demonstrated portal venopathy. No endothelial hyperplasia was seen at any stage of the experiments thus eliminating the probability of peliosis being a source of vascular neoplasia, which has previously been described following more prolonged exposure to DMN. Certain parallelisms of the experimental results with hepatic vascular lesions in man subjected to drug therapy are discussed.
D000284:Administration, Oral; D000818:Animals; D006224:Cricetinae; D004128:Dimethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D011169:Portal Vein / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D004128:Dimethylnitrosamine