Hormonal effects on thymidine kinase and thymidylate kinase activity of estrogen-dependent tumors in the rat.

In estrogen-induced, estrogen-dependent, mammary and adrenocorlical carcinomas, the specific activities of t lie tliymidine kinasc and thymidylate kinase decreased significantly within 2 to 4 days after removal of the source of estrogen of the host. After 7 days, these changes were even more marked in the adrenal tumors. Similar changes were not observed in the activity of these enzymes in autonomous tumors in response to alterations in the supply of estrogen to the host. The treatment with antiestrogenic compounds of estrogenized animals bearing dependent adrenal tumors also caused a decrease in the activity of the two enzymes. The replacement of estrogen by treatment with adrenocorticotropic hormone in animals with adrenal tumors caused a stimulation of kinase activity at 2 days but did not prevent the decrease observed at 7 days after the removal of estrone. Growth of the mammary and adrenocortical carcinomas, as indicated by activity of the kinases, was maintained after estrogen removal by treatment of the host with prolactin. investigate this possibility. The effects of estrogen withdrawal on the growth rate of dependent and autonomous mammary and adrenocortical carcinomas have been studied, and attempts to maintain the growth of dependent tumors in the absence of estrogen by administering other hormones are also described. In these experiments, the activities of 2 enzymes associated with DNA precursor synthesis, the thymidine and thymidylate kinases, have been used as indicators of tumor growth rate. Previously, it has been shown that the activity of the thymidine kinase varied with growth rate of the adrenocortical tumors and that the activity of the enzyme decreased rapidly on removal of the estrogen from the host (7). This decrease occurred significantly before changes in physical dimensions could be reliably detected. In these studies, the thymidylate kinase has been included to provide an additional indication of the rate of growth of the tumor and to supplement the information obtained by measuring the tliymidine kinase, since the significance of the latter enzyme in cellular metabolism is not known.