The effect of 2-aminofluorene and related aromatic amines on the protein and ribonucleic acid metabolism of liver slices

Abstract

The effects of some aromatic amines on the protein and ribonucleic acid metabolism in liver and kidney slices from rats and guinea pigs were investigated. 1. 1. The incorporation of 14C-valine into protein by rat liver slices was markedly inhibited by 2-aminofluorene (AF) and 2-acetylaminofluorene (AAF), which have a carcinogenic effect on rat liver. 2. 2. The non-carcinogenic aromatic amines aniline and 1-aminonaphthalene (1-AN) did not inhibit the incorporation of 14C-valine into protein by rat liver slices under similar conditions. 3. 3. The bladder carcinogen 2-aminonaphthalene (2-AN), which like most other aromatic amines is metabolized by liver, inhibited the incorporation of 14C-valine into protein by rat liver slices at least as much as did AF and AAF. 4. 4. In slices from guinea pig, an animal which is refractory to the carcinogenic effect of AF and AAF, these compounds inhibited the incorporation of 14C-valine into protein even more than in rat liver slices. 5. 5. Substitution of fluorine in position 7 of the AF molecule, which increases the carcinogenicity of this compound in liver, rather decreased the inhibitory effect in rat liver slices. A similar picture was observed with guinea pig slices, although the difference in this case was less pronounced. 6. 6. A certain time of preincubation was needed for the inhibitory effects to become manifest. The incorporation of 14C-valine into protein by rat kidney slices was not inhibited by the above compounds. These facts suggest that the true inhibitors were metabolitic derivatives of the administered substances. 7. 7. The incorporation of 14C-adenine into ribonucleic acid by rat liver slices was inhibited by AF, FAF and 2-AN under the same conditions as the valine incorporation, although to a somewhat lesser extent.