Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines

Abstract

Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19–0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations focusing on the detection of DSB for predicting individual response to radiation therapy for dogs, regardless of tumor type.

Identifying Candidate Druggable Targets in Canine Cancer Cell Lines Using Whole-Exome Sequencing

“…This study is the first report of next-generation sequence analyses across this panel of 33 canine cancer cell lines. These cell lines have been previously used for preclinical screening of therapeutics to assess their potential for use in the treatment of spontaneous canine cancer (10,30,31). We found that the mutational burden of these cell lines varied from 15.79 to 129.37 mutations per MB.…”

Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure

“…Immediately after irradiation, cells were trypsinized and replated. The first post irradiation metaphase cells were harvested with 0.1 μg/mL Colcemid (Invitrogen Life Technologies) treatment and prepared as a standard method [ 57 ]. Samples were treated in 75 mM KCl solution for 20 min at 37 °C and fixed in 3:1 (methanol: acetic acid) Carnoy fixation solution three times.…”

Comparative Mathematical Radiotherapy of Some Dog and Human Cancers

“…Combination of doxorubicin, cisplatin vinblastine or cyclophosphamide with radiotherapy of tonsillar squamous carcinoma of dog yielded a favourable higher rate of therapeutic response and signi cantly longer survival times [54]. But radiotherapy is a viable alternative for the palliative treatment of canine oral melanoma [43], in spite of the fact that hypoxia has negative in uence on determining response to conventional therapy [56], suggesting that substantial differences in intrinsic radio-sensitivity exist in canine cancers [57]. Fluorodeoxyglucose (FDG)/PET is an effective imaging technique for lymph mode staging of locally advanced cervical carcinoma with negative computed tomography (CT) ndings, despite PET-CT could customize and guide brachytherapy planning [58].…”