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

Journal Article · Thu Jul 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.12.062· OSTI ID:21436049

Urano, Muneyasu ^[1]; Fuqiu, He; Minami, Akiko ^[1]; Ling, C Clifton ^[2]; Li, Gloria C ^[1]

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1. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
2. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

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-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.

• OSTI ID: 21436049
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 77, 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.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

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