Increased Photosensitivity in HL60 Cells Expressing Wild-Type p53 |
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Authors: | Anita M. R. Fisher Kathleen Danenberg Debabrata Banerjee Joseph R. Bertino Peter Danenberg Charles J. Gomer |
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Affiliation: | Clayton Ocular Oncology Center, Childrens Hospital Los Angeles, Los Angeles, CA, USA;departments of Biochemistry &Molecular Biology;Pediatrics Radiation Oncology, Molecula Pharmacology &Toxicology, University of Southern California, Los Angeles, CA, USA;Molecular Pharmacology &Therapeutics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA |
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Abstract: | 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 pho-todynamic therapy has not been reported. In the current study we examined photosensitivity in human promye-locytic 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 photo-sensitizer. 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-medi-ated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells . |
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