Nucleotide interconversions. IV. Activities of deoxycytidylate deaminase and thymidylate synthetase in normal rat liver and hepatomas.

Normal and neoplastic rat liver was analyzed for deoxycytidylate deaminase and thymidylate synthetase. For these assays, highly sensitive radiochemical methods capable of detecting the formation of less than 0.001 /~mole of deoxyuridylate and thymidylate were employed. Deoxycytidylate deaminase was found in normal adult rat liver, rat embryo liver, regenerating liver, Novikoff hepatoma, Dunning hepatoma, and the Morris 51~3 hepatoma, sublines A, B, and C. The deaminase varied in activity from a low of '2 gmoles of deoxyuridylate formed/gm protein/hour for adult rat liver to a high of 750 gmoles formed/gin protein/hour for the Novikoff hepatoma. The results suggest the possibility of a correlation between growth rate and deaminase activity. Thymidylate synthetase was less variable in activity, ranging from 2 to 1~ ~moles of thymidylate formed/gin protein/hour. This enzyme was measurable in all the tissues studied except in normal adult rat liver. Analysis of the compounds obtained by conducting the deaminase assay in the presence and absence of fluoride revealed interesting differences in the tissues mentioned above. The apparent enhanced deoxyeytidylate deaminase activity in extracts of the Novikoff, Dunning, and Morris 51s (subline B) hepatomas, incubated in the absence of fluoride, was due to a nucleoside deaminase. This activity could not be detected with deoxycytidine-~-C ~4 as substrate in extracts of the other tissues. The apparent phosphatase activity in regenerating liver and rat embryo liver extracts, as determined from ion-exchange elution patterns, was appreciably lower than that in normal adult rat liver and the various neoplasms studied. These results have been confirmed by measuring phosphate release from various deoxynucleoside 5'phosphates.