FINE STRUCTURAL ALTERATIONS IN CELL PARTICLES DURING CHEMICAL CARCINOGENESIS

Abstract

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 ⇌ α-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.