Studies on the anti-tumour activity of aliphatic aldehydes. V. Preferential inhibition of protein synthesis in normal or neoplastic tissues in relation to molecular structure

The in vitro study of kinetics of the incorporation of labelled amino acids into protein of normal and neoplastic tissues has demonstrated that l-erythro-α,β-dihydroxybutyraldehyde (l-erythro-DHBA), at concentrations which do not appreciably affect cell respiration, inhibits in a preferential way protein synthesis in tumours. In the presence of 5 mM l-erythro-DHBA, the leucine incorporation into protein of a large number of tumours is completely inhibited during the 2nd hr of incubation. Under the same experimental conditions, the amino acid incor poration rate into protein of various normal tissues decreases as compared to controls, but it is never blocked. A relationship between the rate of protein synthesis and the sensitivity to the aldehyde has been observed in normal tissues but not in tumours. The tumours are affected by the drug independently of their histogenetic origin. l-erythro-DHBA is not the only substance which acts preferentially on tumours. The comparative study of the effect of various 3- and 4-carbon aliphatic aldehydes on the in vitro leucine incorporation into protein of rat liver and Yoshida ascites hepatoma has demonstrated that α-hydroxybutyraldehyde, β-hydroxybutyraldehyde, α,β-dihydroxybutyraldehyde and its structural isomers are more active on the hepatoma than on the liver, while propionaldehyde, lactaldehyde, glyceraldehyde, n-butyraldehyde, iso-butyraldehyde, crotonaldehyde, and α-methylglyceraldehyde are more active on the liver than on the hepatoma. A complete inhibition of protein synthesis during the 2nd hr of incubation has been observed in the rat liver in the presence of 5 mM iso-butyraldehyde. On the whole, this data leads one to conclude that the branching of the carbon chain in the C4-aldehydes increases their selective toxicity for the liver, whereas the hydroxylation of the straight chain in the above-mentioned aldehydes gives rise to substances with a preferential action against tumours.