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J. Biophys. and Biochem. Cytol., Vol 10, 23-36, Copyright © 1961 by Rockefeller University Press

ARTICLE

FINE STRUCTURAL ALTERATIONS IN CELL PARTICLES DURING CHEMICAL CARCINOGENESIS : III. Selective Action of Hepatic Carcinogens Other than 3'-Methyl-4-Dimethylaminoazobenzene on Different Types of Mitochondrial Swelling. Effect of Stimulated Liver Growth



Joseph C. Arcos D.Sc.1, Hans H. Gosch 1, and David Zickafoose 1

1 From the Cancer Research Laboratory, Department of Pharmaceutical Chemistry, The J. Hillis Miller Health Center, University of Florida, Gainesville.

Dr. Arcos' and Mr. Gosch's present address is Research Laboratory, United States Public Health Service Hospital, New Orleans, and Tulane University School of Medicine, New Orleans

The previous studies on the correlation between tumor incidence and changes in microsomal and mitochondrial swelling during feeding of 3'-methyl-4-dimethylaminoazobenzene to rats have been extended to other hepatic carcinogens. Administration of 4'-fluoro-4-dimethylaminoazobenzene, 4'-ethyl-2-methyl-4-dimethylaminoazobenzene, 2-acetylam-inofluorene, ethionine, and tannic acid were found to produce drastic alterations of the swelling of rat liver mitochondria. In contrast to these compounds, feeding of the non-carcinogenic azobenzene and 4-diethylaminoazobenzene produced only small changes in swelling. Significant modification in the over-all pattern of the swelling curve was observed when the usual concentration of 3'-methyl-4-dimethylaminoazobenzene was reduced, but not when the riboflavin level in the diet was increased tenfold. Feeding of high levels of this dye to the guinea pig did not affect mitochondrial swelling which is consistent with the resistance of this species to azo-dye carcinogenesis. Hypophysectomy provides protection against the alterations, produced by feeding 3'-methyl-4-dimethylaminoazobenzene, in the characteristics of thyroxine- or mercuric chloride-induced mitochondrial swelling. Studies with citric cycle substrates on mitochondrial swelling suggest block of the glutamate rlhar2 alpha-keto-glutarate pathway after feeding 3'-methyl-4-dimethylaminoazobenzene for 4 weeks. There is a considerable, but reversible, reduction of certain types of mitochondrial swelling in two situations associated with rapid liver growth: after partial hepatectomy and after intraperitoneal injection of 20-methylcholanthrene. Naphthacene, however, which also stimulates rapid liver growth, does not affect mitochondrial swelling.

Submitted on October 21, 1960


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