A comparative study of in vivo RNA and protein synthesis in rat liver and lung.

pharmacologically active substances (23). It is also recognized that the lung contains enzymatic systems capable of metabolizing foreign compounds (3, 11, 55), although their oi'erall importance is considered to be rather small (38). Nevertheless, the induction of aryl hydrocarbon hydroxylases in lung by polycyclic hydrocarbons and other compounds (11, 59†" 61)and the inhibition of this adaptive mechanism by at least 1 well-known pulmonary carcinogen, nickel carbonyl (50), are of great interest. The broader aspects of pulmonary protein metabolism (29, 30) and the biochemical reactions of 1 pulmonary cell type exposed to a number of noxious agents in vitro have already attracted some interest (10, 32, 35, 39). This situation encouraged us to investigate some aspects of pulmonary biochemistry in the intact animal. We attempted to evaluate RNA and protein synthesis in pulmonary tissue, measured with the incorporation of suitable radioactive precursors into these macromolecules in vivo. The liver served in all studies as a control organ, and a few metabolic inhibitors, for which the effect on hepatic RNA and protein metabolism are well known, were also utilized in order to evaluate similarities and dissimilarities between lung and liver. MATERIALS AND METHODS Radiochemicals. Uridine-2-' 4C (specific activity, 50 to 65 mCi/mmole), orotic acid-6-' 4C (specific activity, 50 to 65 mCi/mmole), DL-aspartic-4-' 4C acid (specific activity, 2.1 mCi/mmole), @ C 5'-monophosphate (specific activity, 24.1 mCi/mmole), uracil-2-'4C (specific activity, 7.1 mCi/mmole), and orotic-carboxyl-' 4C acid (specific activity, 10.2 mCi/mmole) were all purchased from New England SUMMARY The incorporation of radioactive orotic acid and uridine into total RNA was measured in vivo in rat liver and lung. Orotic acid labeled hepatic RNA 10 times higher than pulmonary RNA. Uridine labeled pulmonary RNA about twice, as did orotic acid, and was incorporated very little into hepatic RNA. Specific activities of total acid-soluble UMP were measured in both organs. Comparison of pool sizes and labeling of RNA suggested that lung was about as effective in synthesizing RNA as was liver in its use of orotic acid as precursor, and it was slightly superior in its use of undine. The activity of enzymes on the main pathway for pyrimidine synthesis (aspartate transcarbamylase and orotidine 5'-phosphate pyrophosphorylase and decarboxylase) was higher in liver high-speed supernatants, whereas uridine kinase and uridine phosphorylase were more active in lung. Actinomycin D and DL-ethionine blocked RNA synthesis in both liver and lung; nickel carbonyl affected hepatic RNA synthesis only ; and …