Response to multiple radiation doses of human colorectal carcinoma cells infected with recombinant adenovirus containing dominant-negative Ku70 fragment. Academic Article uri icon

Overview

abstract

  • 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 approximately 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-transfected 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.

publication date

  • July 1, 2010

Research

keywords

  • Adenoviridae
  • Antigens, Nuclear
  • Colorectal Neoplasms
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins
  • Defective Viruses
  • Radiation Tolerance

Identity

PubMed Central ID

  • PMC2879402

Scopus Document Identifier

  • 77952571721

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2009.12.062

PubMed ID

  • 20510198

Additional Document Info

volume

  • 77

issue

  • 3