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. Comparable analysis of p53 status with sensitivity to oxidative stress induced by photodynamic therapy has not been reported. In the current study we examined photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)-based photosensitizer. Total SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation conditions could be adjusted to achieve equivalent cellular PH levels during experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2-mediated photosensitization, as well as to UVC irradiation, when compared to HL60 cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response was observed following purpurin- and porphyrin-induced photosensitization in all cell lines. Results of this study indicate that photosensitivity is increased in HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells.
Fisher
A M
AM
Clayton Ocular Oncology Center, Childrens Hospital Los Angeles, CA 90027, USA.
Danenberg
K
K
Banerjee
D
D
Bertino
J R
JR
Danenberg
P
P
Gomer
C J
CJ
D002470:Cell Survival; D018922:HL-60 Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D011166:Porphyrins / Q000378:metabolism; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; C063166:tin etiopurpurin