Effects of aliphatic aldehyde metabolism on protein synthesis and thiol compounds in rat liver and hepatoma induced by 4-dimethylaminoazobenzene

The effects of isobutyraldehyde and 2,3-dihydroxybutyraldehyde on protein synthesis, adenosine triphosphate, non-protein sulfhydryl compounds and glutathione levels, as well as the metabolic rate of some aliphatic aldehydes, were studied in slices of rat liver and hepatoma induced by 4-dimethylaminoazobenzene. Aliphatic aldehydes depressed protein synthesis in liver and hepatoma cells but not in polysomes translating endogenous messenger RNA. During 4-dimethylaminoazobenzene carcinogenesis, the inhibitory effect of isobutyraldehyde on protein synthesis gradually decreased, while that of 2,3-dihydroxybutyraldehyde increased. Aldehydes caused a shifting of the cytosolic oxidation-reduction state and a diminution of adenosine triphosphate concentration in the liver. These modifications did not occur in the hepatoma, where the rates of aldehyde metabolism and aldehyde dehydrogenase activity were greatly reduced in comparison to those of the liver. Aldehydes caused a diminution of the levels of nonprotein sulfhydryl compounds and reduced glutathione in liver and hepatoma, and the lowest values were observed in hepatoma in the presence of 2,3-dihydroxybutyraldehyde. These results suggest that the inhibition of protein synthesis in rat liver is mainly related to the shifting of the cytosolic oxidation-reduction state connected with aldehyde oxidation, whereas in hepatoma it is due, at least in part, to a depletion of thiol compounds.