title: Decrease in the frequency of X-ray-induced mutation by wild-type p53 protein in human osteosarcoma cells.
abstract: Tumor suppressor p53 protein acts as a checkpoint factor following DNA damage. Inactivation of checkpoint control may increase the frequency of mutation following DNA damage, resulting in tumor progression. Here we examine whether wild-type (wt) p53 protein suppresses X-ray-induced mutations using an isopropyl-beta-D-thiogalactopyranoside (IPTG)-regulated p53 expression system in human osteosarcoma Saos-2 cells. Frequency of X-ray-induced mutations in the hypoxanthine-guanine phosphoribosyl transferase gene was enhanced about 10 and 20 times by 1 and 2 Gy respectively in cells without expression of wt p53 protein, while enhancement of mutations by X-rays was slight in cells with expression of wt p53 protein. Furthermore, arrest at the G/S boundary was induced by X-ray irradiation when p53 protein was expressed by treatment with IPTG. These findings suggest that wt p53 protein has a function in maintaining genomic stability after X-ray irradiation through the G1 checkpoint and loss of p53 function(s) may lead to tumor progression in multi-step tumorigenesis.
authors.affiliation: Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Sakyo-ku, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamagishi
authors.forename: J
authors.initials: J
authors.lastname: Miyakoshi
authors.forename: H
authors.initials: H
authors.lastname: Takebe
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002999:Clone Cells; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014965:X-Rays
chemical_list: D016159:Tumor Suppressor Protein p53; D007041:Hypoxanthine Phosphoribosyltransferase