Studies on Thymidine Kinase of Human Liver Cells in Culture

From the ¹ From Norsk Hydro's Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway

The multiplication of Chang human liver cells in tissue culture was inhibited by deoxythymidine in concentrations higher than 0.03 mm, an effect which could be prevented by deoxycytidine as long as the concentration of deoxythymidine was not higher than 0.5 mm.

Attempts were made to induce thymidine kinase by growing the liver cells in the presence of exogenous deoxythymidine. Only slight increases in thymidine kinase activity were found in these experiments.

A marked increase in specific activity of thymidine kinase was observed when the liver cells were grown in a medium supplemented with amethopterin or 5-fluorodeoxyuridine. The increase in kinase activity caused by amethopterin could be prevented and reversed by adding deoxythymidine to the culture medium. Data are presented indicating that the amethopterin-induced elevation of thymidine kinase activity results from synthesis of new enzyme protein.

The results indicate that one, or more, of the phosphorylated derivatives of deoxythymidine controls the synthesis of thymidine kinase of Chang liver cells by repression.

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