An Ultrastructural Study of the Toxic and Carcinogenic Effects of 2-Amino-5- azotoluene on the Livers of Schistosome-infected and -uninfected Mice

Female CBA mice were divided randomly into 4 groups: (a) controls; (b) mice given injections of a carcinogen (2-amino-5-azotoluene); (c) mice exposed to cercariae of Schistosoma mansoni; and (d) mice receiving both the carcinogen and Schistosoma mansoni. At 4 intervals, representative samples of liver from 3 or 4 animals in each group were prepared for electron microscopic study. Five of 13 hepatomas that appeared in group d were similarly studied. The single hepatoma that developed in group b was too small for such study and no tumors arose in groups a and c. All of the tumors examined exhibited an ultrastructural organization analogous to that of hepatic parenchymal cells. Changes noted in liver cells of the carcinogen-treated group included: disorganization of the rough endoplasmic reticulum, hypertrophy of the smooth endoplasmic reticulum, development of “sheaves” of smooth-surfaced cylinders, depletion of glycogen, formation of autophagic vacuoles, changes in mitochondrial size and shape, and sporadic alterations of the nuclei and nucleoli. These abnormalities were more prevalent and more severe in mice that received the carcinogen alone than they were in the animals that were both carcinogen-treated and schistosome-infected, yet the development of hepatomas was more manifest in the latter group than it was in the former. The results are considered to support the view that toxic morphologic alterations produced in the liver by hepatocarcinogens are not necessarily related to tumor induction.