INCREASED PHOTOSENSITIVITY IN HL60 CELLS EXPRESSING WILD-TYPE P53

Loss of p53 function has been correlated with decreased sensitivity to chemotherapy and radiation therapy in a variety of human tumors. Comp arable analysis of p53 status with sensitivity to oxidative stress ind uced by photodynamic therapy has not been reported. In the current stu dy we examined photosensitivity in human promyelocytic leukemia HL60 c ells exhibiting either wild-type p53, mutated p53 or deleted p53 expre ssion. Experiments were performed using a purpurin, tin ethyl etiopurp urin (SnET2)-, or a porphyrin, Photofrin (PH)based photosensitizer. To tal SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation con ditions could be adjusted to achieve equivalent cellular PH levels dur ing experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensit ive to PH- and SnET2-mediated photosensitization, as well as to UVC ir radiation, when compared to HL60 cells exhibiting deleted or mutated p 53 phenotypes. A rapid apoptotic response was observed following purpu rin- and porphyrin-induced photosensitization in all cell lines. Resul ts of this study indicate that photosensitivity is increased in HL60 c ells expressing wild-type p53 and that photosensitizer-mediated oxidat ive stress can induce apoptosis through a p53-independent mechanism in HL60 cells.