Radiosensitization of Human Cervical Cancer Cells by Inhibiting Ribonucleotide Reductase: Enhanced Radiation Response at Low-Dose Rates

Journal Article · Fri Jul 15 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2011.01.034· OSTI ID:21587600

Colussi, Valdir C ^[1]; Pink, John ^[2]; Radivoyevitch, Tomas ^[3]; Oleinick, Nancy L ^[1]

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1. Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States)
2. Department of General Medical Sciences, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States)
3. Department of Epidemiology and Biostatistics, Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States)

Purpose: To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator. Methods and Materials: The cells were exposed to low-dose-rate radiation (11, 23, 37, 67 cGy/h) using a custom-fabricated cell irradiator or to high-dose-rate radiation (330 cGy/min) using a conventional cell irradiator. The radiation sensitivity of human cervical (CaSki, C33-a) cancer cells with or without RNR inhibition by 3-AP was evaluated using a clonogenic survival and an RNR activity assay. Alteration in the cell cycle distribution was monitored using flow cytometry. Results: Increasing radiation sensitivity of both CaSki and C33-a cells was observed with the incremental increase in radiation dose rates. 3-AP treatment led to enhanced radiation sensitivity in both cell lines, eliminating differences in cell cytotoxicity from the radiation dose rate. RNR blockade by 3-AP during low-dose-rate irradiation was associated with low RNR activity and extended G{sub 1}-phase cell cycle arrest. Conclusions: We conclude that RNR inhibition by 3-AP impedes DNA damage repair mechanisms that rely on deoxyribonucleotide production and thereby increases radiation sensitivity of human cervical cancers to low-dose-rate radiation.

• OSTI ID: 21587600
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 80, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2011.01.034; PII: S0360-3016(11)00201-X; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CELL CYCLE
DNA DAMAGES
DOSE RATES
ENZYME INHIBITORS
IONIZING RADIATIONS
IRIDIUM 192
IRRADIATION
NEOPLASMS
RADIATION DOSES
SENSITIVITY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DOSES
ELECTRON CAPTURE RADIOISOTOPES
HEAVY NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IRIDIUM ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
RADIATIONS
RADIOISOTOPES
YEARS LIVING RADIOISOTOPES