Arginine synthesis by hepatomas in vitro. I. The requirements for cell growth in medium containing ornithine in place of arginine and the isolation and characterization of variant hepatomas auxotrophic for arginine

Abstract

Cell growth in ‘ornithine-medium’ requires the expression of two liver-specific genes, those for ornithine transcarbamoylase (OTC) and carbamoyl phosphate synthetase I (CPS-I). CPS-II appears unable to replace CPS-I in this system. The need for N-acetylglutamate (to activate CPS-I) can be met, at least in part, by providing it in the medium. The other gene products involved in arginine biosynthesis are probably all ubiquitous (i.e. not tissue-specific). In an attempt to study the factors responsible for the expression of liver-specific genes, variant hepatomas are isolated that have lost the ability to grow in ornithine-medium. Two classes of ‘orn-’ variants are identified: unstable variants that require dexamethasone for adequate CPS-I production, and ‘stable’ variants that have lost many liver-specific traits. Studies on one stable variant show that it can revert (though rarely), and that it regains its various liver-specific traits in a non-coordinate fashion.