IN a previous paper (Barnes and Magee, 1954) some toxic properties of dimethylnitrosamine (DMN) were described. It was found that rats and other animals suffer severe liver damage after the administration of DMN in doses of the order of 25 mg. per kilogram body weight, either orally or parenterally. The liver lesion was an extensive centrilobular type of necrosis, involving all lobules; followed by evidence of regeneration in surviving animals. An outstanding feature of the necrosis was its very haemorrhagic character and the liver lesion was frequently accompanied by massive haemorrhagic ascites and bleeding into the gastro intestinal tract.These features of the acute liver necrosis were similar to those produced by the senecio alkaloids in rats (Davidson, 1935). A recent paper (Schoental, Head and Peacock, 1954) showed that senecio alkaloids also produced liver tumours if they were administered over longer periods. It seemed possible, therefore, that the chemically much simpler molecule DMN might also produce liver tumours in rats. The present paper describes the results of a long-term feeding experiment in which the compound was added to the diet of rats. A smaller and shorter experiment on rabbits was also performed. In the rats a very high incidence of hepatic tumours occurred, many with metastatic spread, but in the rabbits no tumours were observed. In no instance were primary tumours found in organs other than the liver.MATERIAL AND METHODS Male and female albino rats and cross-bred male rabbits were used. The basal diets were M.R.C. Diet 41 (Bruce and Parkes, 1949) for the rats and M.R.C. Diet 18 (Bruce, 1947) for the rabbits. The diet was given in powder form. DMN was made up as a solution in arachis oil so that 10 ml. added to 1 kg. of powder gave the required concentration.The food intake of the rats was measured for each cage of 5 animals by filling the container each day and measuring the unconsumed residue.The animals were weighed weekly and observed each day when their food was being measured. Post mortems were carried out on all animals that were either found dead or killed by coal gas when seriously ill. Tissues were fixed in Helly's fluid and formol-saline, embedded in paraffin and sectioned at 5,s. All sections were stained with haematoxylin and eosin as a routine and selected material was stained by Mallory's connective tissue method, Gomori's silver impregnation, and
No abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.