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Int. J. Mol. Sci. 2019, 20(4), 841; https://doi.org/10.3390/ijms20040841

Radiobiological Characterization of Canine Malignant Melanoma Cell Lines with Different Types of Ionizing Radiation and Efficacy Evaluation with Cytotoxic Agents

1
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
2
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
3
Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba 263-8555, Japan
4
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
5
Cell Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA
*
Author to whom correspondence should be addressed.
Received: 1 February 2019 / Revised: 12 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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Abstract

Canine malignant melanoma (CMM) is a locally and systemically aggressive cancer that shares many biological and clinical characteristics with human mucosal melanoma. Hypofractionated radiation protocols have been used to treat CMM but little is known about its radiation biology. This pilot study is designed to investigate response of CMM cell lines to various ionizing radiations and cytotoxic agents to better understand this canine cancer. Four CMM cell lines were evaluated by clonogenic survival assay under aerobic and hypoxic conditions and parameters such as alpha beta (α/β) ratio, oxygen enhancement ratio (OER), and relative biological effectiveness (RBE) were calculated after 137Cs, 6 megavoltage (MV) photon, or carbon ion irradiation. Six cytotoxic agents (cisplatin, camptothecin, mitomycin C, bleomycin, methtyl methanesulfonate and etoposide) were also assessed for their efficacy. Under aerobic condition with 6 MV photon, the α/β ratio of the four cell lines ranged from 0.3 to >100, indicating a wide variation of cellular sensitivity. The ratio increased under hypoxic condition compared to aerobic condition and this was more dramatic in 137Cs and 6 MV photon treatments. OER of carbon was lower than 137Cs at D10 in 3 of the 4 cell lines. The RBE values generally increased with the increase of LET. Different cell lines showed sensitivity/resistance to different cytotoxic agents. This study revealed that CMM has a wide range of radiosensitivity and that hypoxia can reduce it, indicating that widely used hypofractionated protocols may not be optimal for all CMM patients. Several cytotoxic agents that have never been clinically assessed can improve treatment outcome. View Full-Text
Keywords: canine malignant melanoma; ionizing radiation; photon; carbon ion; tumor hypoxia canine malignant melanoma; ionizing radiation; photon; carbon ion; tumor hypoxia
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Yoshikawa, H.; Sunada, S.; Hirakawa, H.; Fujimori, A.; Elmegerhi, S.; Leary, D.; Kato, T.A. Radiobiological Characterization of Canine Malignant Melanoma Cell Lines with Different Types of Ionizing Radiation and Efficacy Evaluation with Cytotoxic Agents. Int. J. Mol. Sci. 2019, 20, 841.

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