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Fine Structural Changes in Hepatocytes after Simultaneous Treatment with Single Doses of 3'-Methyl-4-dimethylaminoazobenzene and Cycloheximide¹

Department of Pathology, University of Bristol, Medical School, University Walk, Bristol, England

Male rats were given single doses p.o. of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), either alone or at the same time as single s.c. injections of cycloheximide. They were killed either 24 or 48 hr after treatment or at intervals up to 21 months, and their hepatic tissues were examined by electron microscopy. Whereas 3'-MeDAB alone induced an early, marked peripheral displacement of organelles in the cytoplasm of the hepatocytes, together with a reduction in hyaloplasmic electron density, combined treatment with both chemicals failed to produce this acute toxic effect. However, the fine structure of the hepatic cells of rats given this combined treatment with cycloheximide and 3'-MeDAB closely resembled that obtained by chronic exposure to carcinogenic azo dyes. Of the changes thus produced, the granular endoplasmic reticulum in particular became permanently altered, both quantitatively and morphologically. Other persistent changes included mitochondrial abnormalities and glycogen depletion. Cycloheximide appears to protect the liver cell against the nonspecific acute toxic action of 3'-MeDAB, while facilitating the expression of effects that may possibly be associated with the carcinogenic action of this azo dye. Although this experimental model does not result in the appearance of tumors, it demonstrates that a single exposure to a carcinogen may induce permanent changes that are similar to those observed during carcinogenesis.

¹ We wish to thank the Cancer Research Compaign for their generous financial support. This is Paper 4 of the series, "Modification of Toxic Liver Injury in the Rat."

² Present address: Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Received 5/ 6/75. Accepted 3/22/76.