PLATES LXXVI-LXXX) IN previous papers (Mazzanti and Lopez, 1951-52, 1952a and b, 1953a and b ) we have reported that alpha-naphthyl-iso-thiocyanate (A.N.I.) , when introduced either orally or parenterally in different doses, with Werent frequencies, by various modes of application and by different vehicles, exerts a serious toxic action on different species of animals.We have described the alterations that appear in certain organs, particularly in the liver, in the first period of treatment. These consist in hypertrophy of the periportal spaces due to cellular proliferation which spreads and penetrates more or less deeply, through the central zones of the hepatic lobules. I n the present paper we report the results of further investigations on protracted treatment with this drug. Proliferation of small bileducts is evident, with regeneration of reticular fibres and formation of young fibroblasts.On the basis of these observations we re-examined the histological sections from the earlier experiments and noted that the changes begin as a proliferation of apparently undifferentiated cellular elements. Development of solid or hollow tubular structures, considered to be regenerated bileducts, is evident in the liver of rats subjected to this protracted treatment.These observations are of some importance in establishing the fact that a chemical substance, whose nature is well known, has a direct stimulating effect on the growth of the bile-duct epithelium.
MATERIALS ANXI XETHODSThe investigations were carried out on 50 male albino rats of the Italic0 strain, weighing, at the beginning of the experiment, between 100 and 150 g. They were given the following standard diet :-whole wheat flour 300 g., whole maize flour 300 g., whole barley flour 300 g., casein 60 g., calcium lactate 30 g., olive oil 20 g. It WBB dissolved in olive oil and added to the diet i n the proportion of 1 g./kg. of mixture. The diet was given ad libitum. Thie dose of A.N.I. allowed the animals to remain in 8 healthy condition. They were killed at intervals ranging from 15 days to 7 months. A.N.I. w&8 obtained from British Drug H o w , Ltd.
243Arch. I&. anat. e h t . pat., xii, 417.