PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 23 Photobiology/Photochemistry/Photodynamic Therapy
Room: Nevada Exhibition Center

(P28-281) G6PD deficient cells exhibit an unique cross sensitivity to PDT and ionizing radiation.

Tuttle, Stephen^*,1, Busch, Theressa¹, Lustig, Robert¹, Biaglow, John¹, ¹ Radiation Oncology, Philadelphia, PA

ABSTRACT-
Glucose-6-phosphate dehydrogenase is the initial and rate limiting enzyme of the oxidative pentose phosphate cycle. G6PD is highly conserved and absolutely expressed across evolution, suggesting it serves an irreplaceable biochemical function. Others have suggested that G6PD is required for cell growth and division, based largely on the ability of DHEA, a chemical inhibitor of G6PD, to block cell division. However, we recently found that DHEA also blocked cell division in G6PD- cell lines. In addition, we have reported that G6PD activity is very low under the normal steady state conditions observed in exponentially growing cells, in vitro. G6PD activity increases proportionately in response to agents that induce oxidant stress, including ionizing radiation and PDT. G6PD- CHO cells are more sensitive to ionizing radiation-induced cell kill then the wild type CHO cell line, K1. K1 cells express mutant p53 and are therefore relatively resistant to -radiation-induced apoptosis. However, we observed a significant incidence of -radiation-induced apoptosis in the G6PD- CHO cell lines. Moreover, at doses ≤ 2Gy, the incidence of -radiation-induced apoptosis accounted for the entire increase in -radiation-induced clonogenic cell death observed in the G6PD- cells. G6PD- CHO cells were also significantly more sensitive to PDT then K1 cells, when either Photofrin II™ or Leutrin® are used as the photosensitizer. Moreover, the mode of PDT-induced cell death was largely apoptosis in response to either photosensitizer. Significantly, cross sensitivity to -radiation and PDT is a relatively unique phenotype of the G6PD- cell lines, i.e., mutant cell lines, such as XRS-5 and L5178Y-S, which exhibit enhanced sensitivity to ionizing radiation are not sensitive to PDT. Based on these data we suggest that G6PD functions as an antiapoptotic protein in cells exposed to oxidant stress.

KEYWORDS: Glucose-6-phosphate dehydrogenase, Redox, Photodynamic Therapy , Apoptosis