Acute and Temporary Inhibition of Thymidine Kinase in Mouse Bone Marrow Cells after Low-dose Exposure

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Abstract
Low-dose whole-body exposure of mice to < 0.01 Gy [gray] .gamma.-rays causes inhibition of incorporation of thymidine or 5-iodo-2-deoxyuridine into DNA of bone-marrow cells in vitro; the effect is maximal in cells at 4 h after exposure and then subsides within about 10 h. This is due to the inhibition of cellular thymidine kinase, which gradually develops to a maximum at 4 h after exposure and again subsides within the next 10 h. This inhibition involves only 35% of the entire cellular enzyme activity and, analogous to the depression of thymidine incorporation into the cells, is only seen when the cells are collected into medium that is buffered to a pH of 7.2-7.4 and contains about 1350 mg NaHCO3/l. Addition of NaHCO3 to the cell homogenate or to the high speed supernatant containing the enzyme, but not to intact cells, failed to produce enzyme inhibition. There is also no depression of 5-iodo-2-deoxyuridine uptake into the intact cells in vitro when the mice are irradiated either shortly before or after i.v. injection of 0.02 mg of procaine chloride. The reversibility of the effect in vivo and in vitro suggests a particular enzyme control mechanism that may be non-specifically triggered by intracellular charges, such as peroxides, and may enhance repair.