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An Ultrasturctural Study of the Toxic and Carcinogenic Effects of 2-Amino-5-azotoluene on the Livers of Schistosome-infected and uninfected Mice¹

Departments of Pathology and Preventive Medicine, School of Medicine, Case Western Reserve University, and Department of Pathology, Cleveland Metropolitan General Hospital, Cleveland, Ohio 44109

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.

¹ This investigation was supported in part by USPHS Research Grant AM-08416 from the National Institute of Arthritis and Metabolic Diseases and by Department of the Army Research Contract DA-49-193-MD-2639 from the U.S. Army Medical Research and Development Command under the auspices of the Commission on Parasitic Diseases of the Armed Forces Epidemiological Board, and in part by Research Career Development Awards K3-GM-22,575 from the National Institute of General Medical Sciences and AI-31,814 from the National Institute of Allergy and Infectious Diseases.

² Present Address: Department of Pathology, Evanston Hospital, Evanston, Illinois 60201.

³ Present Address: Philippines General Hospital, Taft Avenue, Manila, Philippines.

Received 8/ 2/68. Accepted 11/29/68.