BIOCFIIMICA ET BIOPHYSICA ACTA 103 BBA 95572 FAILURE OF X-RAYS AND ACTINOMYCIN D TO PREVENT THE RESPONSE OF RENAL AND HEPATIC THYMIDYLATE KINASE TO THYMIDINE TREATMENT IN VIVO S. J. ADELSTEIN AND H. I. KOHN Departments o/ Anatomy and Radiology, Harvard Medical School, Boston, Mass. (U.S.A.) (Received October 3rd, 1966) SUMMARY Thymidylate kinase activity was assayed in the supernatant extracts of liver and kidney from adult rats previously injected with thymidine. Prior X-ray and actinomycin D treatment did not affect the increased level of activity found I h after the deoxyribonucleoside was administered. Starvation up to 72 h also had little if any influence on the response to thymidine. Thus, the elevations of thymidylate kinase activity found after hepatectomy or thymidine injection are disparate in their reaction to X-ray and actinomycin D treatment. The thymidine response also differs from other substrate-responsive en- zyme systems in rat liver. INTRODUCTION Subtotal hepatectomy or uninephrectomy initiates a series of cytochemical re- sponses that ultimately lead to compensatory hyperplasia. Among the earliest re- corded events is an increase in the soluble enzymes that convert thymidine to thymidine phosphates and DNA (refs. 1,2). The increase in one of these enzymes, thymidylate kinase, is prevented wholly or in part by I000 rad of X-rays or by actinomycin D administered before or shortly after partial hepatectomy 3-s. The in- corporation of orotic acid into rapidly labeled RNA is also inhibited by I000 rad of X-rays. It has been postulated, therefore, that the rise in the enzyme following hepatectomy depends upon messenger RNA formation and an increased synthesis of the kinase protein 6. On the other hand, an increase in liver and kidney thymidylate kinase activity is also observed when a large dose of thymidine is administered intraperitoneally to rats 7,s. This effect may be due to the stabilization of the existing enzyme by thymi- dylate, since thymidine and thymidylic acid will prolong the activity of the kinase preparation when added to it in vitro 9. Biochim. Biophys. Acta, 138 (1967) I63-I68