Effect of diethylnitrosamine on the livers of rats after high oral doses administered at intervals varying between three and twenty-four days.
When 200 mg of diethylnitrosamine per kg of body weight was administered with a stomach tube once a week to female Wistar W.64 rats, all of them died within three weeks from severe hepatocellular injuries and haemorrhages of the liver, lungs and small intestine. Weekly administrations of 100 mg per kg of body weight consistently caused the rats to die after seven to fifteen weeks from severe hepatic cirrhoses characterized by large tubercles. Weekly doses of 50 mg per kg of body weight caused much less severe hepatic cirrhosis. Under these conditions death occurred after 17 to 23 weeks, all the rats having contracted multiple hepatocellular carcinomas and in most cases pronounced hepatic cirrhosis. When this amount of diethylnitrosamine was administered for twelve weeks only the hepatic cirrhosis was less apparent, but a substantial influence on the tumor development was not observed. After a reduction of the dose to 25 mg per kg of body weight once a week all the rats in the relevant group died after 26 to 35 weeks, likewise from multiple hepatocellular carcinomas. Hepatic cirrhosis were then relatively inconspicuous. Similar results were obtained when, not the dose, but the interval between doses (100 mg/kg each) was varied. This clearly differential effect of diethylnitrosamine in the rat thus makes it a simple matter to induce hepatic cirrhosis or cancers that are suitable for a variety of tests and also, for example, as models for therapy trials.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced*; D008113:Liver Neoplasms / Q000139:chemically induced*; D009374:Neoplasms, Experimental; D009602:Nitrosamines / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D009602:Nitrosamines