DECREASE IN THE FREQUENCY OF X-RAY-INDUCED MUTATION BY WILD-TYPE P53 PROTEIN IN HUMAN OSTEOSARCOMA CELLS

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. Her e we examine whether wild-type (wt) p53 protein suppresses X-ray-induc ed mutations using an isopropyl-beta-D-thiogalactopyranoside (IPTG)-re gulated p53 expression system in human osteosarcoma Saos-2 cells, Freq uency of X-ray-induced mutations in the hypoxanthine-guanine phosphori bosyl transferase gene was enhanced about 10 and 20 times by 1 and 2 G y respectively in cells without expression of wt p53 protein, while en hancement of mutations by X-rays was slight in cells with expression o f wt p53 protein, Furthermore, arrest at the G(1)/S boundary was induc ed by X-ray irradiation when p53 protein was expressed by treatment wi th IPTG, These findings suggest that wt p53 protein has a function in maintaining genomic stability after X-ray irradiation through the G(1) checkpoint and loss of p53 function(s) may lead to tumor progression in multi-step tumorigenesis.