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

Summary

Low-dose whole-body exposure of mice to less than 0·01 Gy γ-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 hours after exposure and then subsides within about 10 hours. This is due to the inhibition of cellular thymidine kinase, which gradually develops to a maximum at 4 hours after exposure and again subsides within the next 10 hours. This inhibition involves only 35 per cent 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 7·2–7·4 and contains about 1350 mg NaHCO₃ per litre. 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 procain 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 changes, such as peroxides, and may enhance repair.