Abstract
Purpose: We have evaluated the physiological functions that supervise radiation-sensitivity of human cells. The functions seem to be regulated by serum factors such as cytokines in the human body. This study examined the involvement of GRP78 in suppression of radiation-induced mutagenic events by interferons in human cells.
Methods: Human RSa cell line and its derivative variant cells, with and without interferons (α or β) treatment, were used for estimation of their susceptibility to UVC- or X-ray-induced phenotypic mutation (increased resistance to 6-thioguanine- or oubain-caused cell-killing) and that of DNA-repair capacity for excision of thymine dimers. Cellular contents of GRP78 were estimated by Western blotting analysis.
Results and discussion: GRP78 has been identified by the mRNA differential display method, as one of genes involved in enhancement of cell mutability by serum derived from pancreatic cancer patients. Variants, which expressed low levels of GRP78, showed higher frequency of phenotypic mutation and lower capacity of DNA excision repair than did the parent cells with normal expression of GRP78. In contrast, high celluar contents of GRP78 were found in interferon-treated cells. These results suggest that GRP78 may play some roles on interferon-induced radiation-resistance in human.
