Suppression of UV-induced mutations by wild-type p53 protein in human osteosarcoma cells

We have examined whether the tumour suppressor p53 protein suppressed UV-induced mutations in the hypoxathine-guanine phosphoribosyl transferase (HPRT) gene and in the supF gene of the shuttle vector plasmid pMY189. We used human osteosarcoma Saos-LP12 cells, in which wild type (wt) p53 protein was induced by treatment with isopopyl-β-D-thiogalactopyranoside. The induction of wt p53 protein suppressed UV-induced mutations but not spontaneous mutations in the HPRT gene. The frequency of UV-induced mutations induced by UV-irradiation of the plasmid was also significantly lower in cells with induced wt p53 protein than in the uninduced cells. In addition, we found that frequency of G: C to A: T transition mutations which occurred at the 3' base pair of dipyrimidine sites were significantly lower in the cells with induced wt p53 protein than in the uninduced cells. These findings suggest that wt p53 protein may play roles in modulating DNA repair pathway, resulting in the suppression of UV-induced mutations.