PARENT SESSION
3:45 PM to 5:15 PM
Tuesday, April 23, 2002
Mini-Symposium 11
DNA Repair and Cytogenetics
Room: Nevada 1-2
, Co-Chair: Brown, Martin¹; Wallace, Susan ²¹Stanford University, Stanford, CA²University of Vermont, Burlington, VA

(MS11-7) DNA Binding Activity of 54 Transcription Factors in Response to Low Dose Fractionated Radiation in Ovarian Carcinoma.

Brandon, Jason^*,1,2, Alcock, Rachael^1,2, Dey, Swatee¹, Sathishkumar, Sabapathi¹, Chendil, Damodaran¹, Mohiuddin, Mohammed¹, Chatfield, Lee², Ahmed, Mansoor¹, ¹ University of Kentucky, Dept of Radiation Medicine, Lexington, Kentucky² University of Central Lancashire, Preston, England

ABSTRACT-
Low Dose Fractionated Radiation Treatment (LDFRT) was found to be a potent chemo-sensitizer in colorectal, head and neck and ovarian tumor cell lines. This study was undertaken to analyze the effects on transcription factor (TF) binding activity in response to single dose radiation (2 Gy), LDFRT (4x 50cGy), Taxotere (TAX, 0.25 nm), TAX + 2 Gy and TAX + LDFRT exposures. BG-1, an ovarian carcinoma cell line, was used for this study, Nuclear extracts were isolated three hours following treatment and DNA binding activity (DBA) of 54 TFs were analyzed using MYRIA Protein/DNA array kit. Out of 54 TFs, DBA of 5 TFs were absent in both untreated and treated groups. DBA of 5 TFs was constitutively expressed with no change in both untreated and treated groups. DBA of the TF Brn-3 was increased by 2 fold and TFs, PPAR, Stat5 and Stat6 were increased by 4 fold in response to 2 Gy. Nine TFs DBA was down regulated in response to 2 Gy exposure. No increase in DBA was found in TAX exposure, however DBA was decreased in 5 TFs. LDFRT caused a 2 fold increase in DBA of 3 TFs and a 4 fold increase of 3 TFs. LDFRT also caused a decrease in DBA of 16 TFs. Interestingly, LDFRT completely inhibited the DBA of TFs, ERE, PRE and TR. TAX plus 2 Gy caused a decreased in DBA of 18 TFs. TAX plus LDFRT caused a decrease in DBA of 26 TFs with complete inhibition of DBA of PRE. Together, the Protein/DNA array analysis of TFs for DBA indicated that LDFRT specifically inhibited the DBA of estrogen response element and progesterone response element, both of which are implicated for ovarian tumor growth. These findings are currently confirmed by electrophoretic mobility gel shift assays and are correlated with clonogenic inhibition in response to these treatments.

KEYWORDS: Ovarian Carcinoma, Low Dose Fractionated Radiation, Taxotere, Transciption Factors