X-irradiation effects on thymidine kinase (TK): II. The significance of deoxythymidine triphosphate for inhibition of TK1 activity
Authors: He, Q.; Skog, S.1; Welander, I.2; Tribukait, B.2
Source: Cell Proliferation, Volume 35, Number 2, April 2002 , pp. 83-92(10)
Publisher: Blackwell Publishing
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Abstract:
. The purpose of this study was to investigate the mechanism behind the high sensitivity of thymidine kinase 1 (TK1) to X-irradiation. The deoxythymidine triphosphate (dTTP) pool was studied in mouse ascites tumour cells 1-24 h after X-irradiation with 5 Gy. Irradiation changed the Michaelis-Menten kinetics of TK1 from linear to biphasic, showing a negative co-operativity. These changes were closely related to changes in the dTTP pool. Addition of dTTP to the cell extract of non-irradiated cells, or thymidine (dTdR) to the culture medium, resulted in changes very similar to the kinetics found in the irradiated cells. Addition of 5¢-amino-5¢-deoxythymidine (5¢-AdTdR), a thymidine analogue that eliminated the inhibitory effect of dTTP on TK1 activity, completely abolished the irradiation-induced inhibition of TK1 activity. We suggest that the reduced TK1 activity is mainly due to an elevated intracellular concentration of dTTP.Document Type: Research article
DOI: 10.1046/j.1365-2184.2002.00227.x
Affiliations: 1: Department of Oncology, KFC, Huddinge University Hospital AB, S-141 86, Stockholm, Sweden and 2: Department of Oncology and Pathology, section Medical Radiobiology, CCK, Karolinska Institute, S-171 76 Stockholm, Sweden
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