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The Incorporation of 5-Iodo-2'-deoxyuridine into the DNA of HeLa Cells and the Induction of Alkaline Phosphatase Activity¹

Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514

Inhibition of DNA synthesis during the period of exposure of HeLa cells to 5-iodo-2'-deoxyuridine (IUdR) inhibited the induction of alkaline phosphatase activity. This finding, taken together with previous findings that IUdR did not induce alkaline phosphatase activity in the presence of 2-fold molar excess thymidine or in a mutant line of HeLa that lacks thymidine kinase, demonstrated that IUdR incorporation into DNA is correlated with the increase in alkaline phosphatase activity. With the exception of an interim period described in the text, induction of alkaline phosphatase activity was linearly related to medium concentrations of IUdR of up to at least 3 µM. However, the extent of IUdR subsitution in DNA did not appear to be related to the degree of enzyme induction. Alkaline phosphatase activity continued to increase at medium concentrations of IUdR from 1 to 3 µM, while little further substitution of DNA occurred.

¹ This investigation was supported by Grant CA16460, awarded by the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 6/28/76. Accepted 8/25/76.