Response to multiple radiation doses of human colorectal carcinoma cells infected with recombinant adenovirus containing dominant-negative Ku70 fragment Journal Article
| Authors: | Urano, M.; He, F.; Minami, A.; Ling, C. C.; Li, G. C. |
| Article Title: | Response to multiple radiation doses of human colorectal carcinoma cells infected with recombinant adenovirus containing dominant-negative Ku70 fragment |
| 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 ∼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. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; human cell; dna-binding proteins; nonhuman; radiation dose; linear models; cytology; animals; dna damage; cell survival; dna repair; genes; radiation; radiotherapy; oxygen; neoplasm proteins; cell line, tumor; transfection; radiation response; radiation dosage; viral gene delivery system; colorectal carcinoma; colorectal neoplasms; feasibility study; dna; genetic transfection; tumors; dosimetry; radiation dose fractionation; irradiation; gene therapy; radiosensitivity; cell hypoxia; rats; virus infection; adenovirus vector; virus recombinant; glass tubes; ku antigen; fractionation; colony-forming units assay; cell strain ht29; ht29 cells; carcinoma cells; nitrogen; repair; adenoviridae; tumor cells; radiation tolerance; cells; colony formation; dna-activated protein kinase; virus cell interaction; dominant-negative ku70; gene-radiotherapy; ku70; potentially lethal damage repair; colorectal cancer cell; damage repair; enhancement ratios; hypoxic cells; linear-quadratic models; multiple-dose; multiplicity of infections; nitrogen gas; oxygen enhancement; rat-1 cells; recombinant adenovirus; single-dose; survival data; surviving fractions; viruses; viral gene therapy; antigens, nuclear; defective viruses |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 77 |
| Issue: | 3 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2010-07-01 |
| Start Page: | 877 |
| End Page: | 885 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2009.12.062 |
| PUBMED: | 20510198 |
| PROVIDER: | scopus |
| PMCID: | PMC2879402 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: IOBPD" - "Source: Scopus" |
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