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Title: Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

Purpose: To investigate the effect of recombinant replication-defective adenovirus containing dominant-negative Ku70 fragment on the response of tumor cells to multiple small radiation doses. Our ultimate goal is to demonstrate the feasibility of using this virus in gene-radiotherapy to enhance the radiation response of tumor cells. Methods and Materials: Human colorectal HCT8 and HT29 carcinoma cells were plated in glass tubes, infected with virus (25 multiplicity of infection), and irradiated with a single dose or zero to five doses of 3 Gy each at 6-h intervals. Hypoxia was induced by flushing with 100% nitrogen gas. The cells were trypsinized 0 or 6 h after the final irradiation, and cell survival was determined by colony formation. The survival data were fitted to linear-quadratic model or exponential line. Results: Virus infection enhanced the radiation response of the HCT8 and HT29 cells. The virus enhancement ratio for single-dose irradiation at a surviving fraction of 0.1 was {approx}1.3 for oxic and hypoxic HCT8 and 1.4 and 1.1 for oxic and hypoxic HT29, respectively. A similar virus enhancement ratio of 1.2-1.3 was observed for both oxic and hypoxic cells irradiated with multiple doses; however, these values were smaller than the values found for dominant-negative Ku70-transfectedmore » Rat-1 cells. This difference has been discussed. The oxygen enhancement ratio for HCT8 and HT29 receiving fractionated doses was 1.2 and 2.0, respectively, and virus infection altered them slightly. Conclusion: Infection of recombinant replication-defective adenovirus containing dominant-negative Ku70 fragment enhanced the response of human colorectal cancer cells to single and multiple radiation doses.« less
Authors:
 [1] ;  [2] ; ;  [1] ;  [3] ;  [1]
  1. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  2. (United States)
  3. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Publication Date:
OSTI Identifier:
21436049
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 77; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2009.12.062; PII: S0360-3016 (10)00012-X; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ADENOVIRUS; CARCINOMAS; FRACTIONATED IRRADIATION; GENES; LARGE INTESTINE; OXYGEN ENHANCEMENT RATIO; RADIATION DOSES; RADIOTHERAPY; TUMOR CELLS ANIMAL CELLS; BODY; DIGESTIVE SYSTEM; DIMENSIONLESS NUMBERS; DISEASES; DOSES; GASTROINTESTINAL TRACT; INTESTINES; IRRADIATION; MEDICINE; MICROORGANISMS; NEOPLASMS; NUCLEAR MEDICINE; ONCOGENIC VIRUSES; ORGANS; PARASITES; RADIOLOGY; THERAPY; VIRUSES