Abstract
Low LET radiation generates toxic free radicals and the resultant free radicals cause injury to nuclear DNA that makes serious damages in living cells. Although endogenous mechanisms to diminish toxicity of the free radicals has been studied in the cell-free system, their functions in the living cells are not clarified. To reveal the initial damages and the protection mechanism, simultaneous measurements of the micronuclei formation and growth arrest in murine macrophage cell line RAW264.7 were performed. Since the glutathion is a major protector for radicals in living cells, we focused on the enzyme glutathion peroxidase (GPx) that catalyzes conversion of glutathion from oxidative to reduced form. A vector that continuously expresses GPx-4 with nuclear localization signal (NLS) peptide sequence at the N-terminal locus was stably introduced into the cells. The frequency of growth arrested cells by radiation was decreased in the most of the transformants. When the NLS was replaced with other signal peptides or removed in the GPx-4 expression vector, the diminishment of the growth arrest was not observed. In any of the transformants, radiation-induced micronucleus rate was not changed. These results show that GPx4 in nucleus leads to cure radiation damages that triggers growth arrest.
