Alteration by phenobarbital and 3-methyl-cholanthrene of functional and structural changes in rat liver due to carbon...

The effect of carbon tetracholoride (CCl4) inhalation (1100 ppm, 30 minutes) on rat hepatic polyribosomal profile, amino acid incorporation and endoplasmic reticulum were studied in phenobarbital or 3-methylcholanthrene (3-MC) pretreated rats. The inhalation of CCl4 alone caused a partial disruption of the hepatic polyribosomal profile. Rats pretreated with phenobarbital or 3-MC showed complete disruption of the hepatic polyribosomal profile. The hepatic polyribosomal profile returned to normal within 24 hours after exposure to CCl4 in saline and 3-MC-pretreated rats as compared to 48 hours in phenobarbital-pretreated rats. The incorporation of 14-C(U)-L-leucine into 9000 x g liver supernatant fraction protein was decreased in phenobarbital-pretreated rats when measured immediately following or 24 hours after inhalation of CCl4. The incorporation was also decreased in 3-MC-pretreated rats when measured immediately after exposure but not at 6 or 24 hours. The centrolobular hepatocytes of phenobarbital-pretreated rats exposed to CCl4 showed dilation and vesiculation of cisternae of the rough endoplasmic reticulum and striking changes in the nuclear double membrane. Partial recovery occurred within 24 hours and complete recovery within 48 hours after exposure. There were no observable changes in these parameters 0, 6, or 24 hours after exposure to CCl4 in 3-MC-pretreated rats. A new hypothesis is put forward which states that the activation of CCl4 to trichloromethyl free radicals takes place at two sites on the reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 electron-transport chain of liver microsomes.