Modification of effects of radiation on thymidine kinase

Thymidine kinase (TdR-K) and the incorporation of iododeoxyuridine (IUdR) into DNA of murine bone marrow cells are acutely and temporarily inhibited by low doses (0.01 Gy) of whole-body gamma-radiation with a maximal effect at 4 h after exposure and full recovery at 10 h. The inhibitory effect was totally abolished by whole-body exposure to a strong static magnetic field of 1.4T. The present investigation was designed to gain insight into the mechanism(s) underlying the inhibition of TdR-K activity and the incorporation of 125I-UdR by challenging the system with various pharmacological and biochemical means. To this end the response of TdR-K and 125I-UdR incorporation into DNA to the administration of actinomycin-D, cycloheximide, cysteamine, misonidazole and procaine hydrochloride as well as to dietary manipulations, i.e. vitamin E deficiency and enrichment of the diet by soya oil, and to changes in the glutathione levels were investigated in bone marrow cells of irradiated and sham-irradiated mice. Furthermore, the effect of various NaHCO3 concentrations on optimizing the radiation-induced inhibition of TdR-K was investigated under conditions of radiation, vitamin E deficiency and enrichment of the diet by soya oil. The data point to the involvement of the cellular radical-detoxification system in changing the activity of TdR-K, especially on the basis of the concurrent increase of glutathione concentration and decrease in TdR-K activity.