The comparative enzymology and cell origin of rat hepatomas. I. Deoxycytidylate deaminase and thymine degradation.

Abstract

SUMMARY Enzyme assays for deoxycytidylate deaminase and catabolism were carried out on ten rat hepatomas, including the Novikoff, Dunning L-C18, McCoy MDAB, and the Morris 3683, 3924A, and 5123 hepatomas, plus primary hepatomas produced by feeding ethionine or 3'-methyl-4-dimethylaminoazobenzene, and hepatomas de rived from the primary tumors induced with ethionine. Normal liver, Dunning L-C18 hepatoma, and Morris 5123 hepatoma were similar in having almost no deoxycytidylate deaminase, whereas the Novikoff hepatoma was shown to be a rich source of the enzyme, converting 400-600 Â?Â?moles substrate/gm protein/hr. Other hepatomas had values between 50 and 500 /umoles/gm protein/hr. The Morris 5123 hepatoma contained thymine reducA­asewith a capacity of 9-23 /Â?moles substrate/gm protein/hr, which was very near the capacity of normal liver. All other hepatomas appeared to lack the capacity to convert carbon 2 of to CO», even in the coenzyme-fortified assay system employed. On the basis of the two enzyme assays mentioned, hepatomas were classified as D+ if the deaminase were present and T+ if the reductase were present, the letter anil sign indicating presence of readily measurable enzyme activity. A tentative chart of relationships was shown, with the hepatomas classified into three types: Novikoff, D+T-; Dunning, D~T-; and Morris 5123, D-T+. The Novikoff rat hepatoma has been studied discovered deoxycytidylate deaminase was found rather extensively and has been shown to lack to be present in the Xovikoff hepatoma and absent many of the enzymes that are found in rat liver (13, from normal adult rat liver (10). However, it was 19), whereas another rat hepatoma, the Dunning present in livers containing large numbers of proL-C18 (4), has been reported to resemble normal liferating bile duct epithelial cells, but absent from liver cells more closely than do the cells of the the Dunning hepatoma (17). The two hepatomas Novikoff hepatoma both microscopically and bio- resembled each other in lacking enzymes for the chemically (16), although still differing consider- reductive catabolism of (21), a process ably from normal or regenerating liver (3, 16). almost exclusively limited to liver, whereas the In contrast to the above studies, the newly Novikoff hepatoma differed from the Dunning „TM..