Prediction of Cellular Radiosensitivity from DNA Damage Induced by .GAMMA.-Rays and Carbon Ion Irradiation in Canine Tumor Cells

Abstract

ABSTRACT. Diseases of companion animals are shifting from infectious diseases to neoplasms (cancer), and since radiation therapy is one of the effective choices available for cancer treatment, the application of radiotherapy in veterinary medicine is likely to increase. However tumor tissues have different radiosensitivities, and therefore it is important to determine the intrinsic radiosensitivity of tumors in individual patients in advance of radiotherapy. We have studied the relationship between the surviving cell fraction measured by a clonogenic assay and DNA double strand breaks detected by a comet assay under neutral conditions in three canine tumor cell lines, after γ-ray and carbon ion irradiation. In all the cell lines, cell death assessed by the clonogenic assay was much higher following irradiation with carbon ions than with γ-rays. The initial and residual (4 hr) DNA damage due to γ-ray and carbon ion irradiation were higher in a radiosensitive cell line than in a radioresistant cell line. The surviving cell fraction at 2 Gy (SF2) showed a tendency for correlation with both the initial and residual DNA damage. In particular, the residual damage per Gy was significantly correlated with SF2, regardless of the type of radiation. This indicates that cellular radiosensitivity can be predicted by detection of radiation-induced residual DNA damage. KEY WORDS: canine tumor cell, comet assay, DNA damage, radiosensitivity, radiotherapy.J. Vet. Med. Sci. 67(11): 1089-1095, 2005 Due to recent improvements in the breeding environment and veterinary preventive medicine, companion animals live much longer than in the past. These improvements have made it possible to reduce severe infectious diseases, but conversely the incidence of tumors is increasing in animals. Radiation therapy is one of the effective choices available against such tumors and its use in veterinary medicine is likely to increase.In human medicine, advances have been made in new technologies, such as low linear energy transfer (LET) radiation using protons [16] and linear accelerator (LINAC) three dimensional X-rays. Because high LET radiation causes higher reproductive cell death than proton irradiation [5], clinical studies of radiation therapy using heavy-ion beams have started. However, a wide range of radiosensitivity is observed, even for tumors of the same histopathological origin [2]. Therefore, to improve local control of the tumor, and to set up an effective treatment plan with minimal side effects, it is necessary to predict the radiosensitivity of the tumor for an individual patient, both for high and low LET radiation. Therefore, development of a predictive assay for tumor radiosensitivity in medical practice and establishment of biological parameters are of importance.In general, the clonogenic survival assay is regarded as a good measure of radiosensitivity related to the effects of radiotherapy [4]. A good correlation has been found between the reproductive death of fibroblasts measured by the clonogenic assay and the severity of...

Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles

“…The results of the present study were consistent with a previous canine cell line study (21). Additionally, several other previous studies using human and rodent cells have demonstrated that high LET heavy ions are more effective for cell killing at identical physical absorbed doses as low LET radiation types (10)(11)(12)21,26). In general, a large number of complex clusters of DNA damage generated by high LET radiation would be more difficult to repair, resulting in more severe biological damage than that induced by low LET radiation (28,29).…”

“…The results of the present study were consistent with a previous canine cell line study (21). Additionally, several other previous studies using human and rodent cells have demonstrated that high LET heavy ions are more effective for cell killing at identical physical absorbed doses as low LET radiation types (10)(11)(12)21,26).…”

Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness

“…Among other radiobiological factors, intrinsic radiation sensitivity of tumour cells represents a major component attributing to treatment outcome [3,[12][13][14]. Intrinsic cellular radiation sensitivity correlates with the number of residual unrepaired DNA double strand breaks (DSBs) [15][16][17]. Therefore, assessment of intrinsic radiation sensitivity through quantification of DNA DSBs has become increasingly utilized in translation cancer research [18][19][20].…”

Predictive and Prognostic Significance of Glutathione Levels and DNA Damage in Cervix Cancer Patients Undergoing Radiotherapy

“…Radiation-induced cell death is attributed mainly to DNA damage (39). Wada et al (40) have reported that the residual DNA damage per Gy obtained by neutral SCGE assay was significantly correlated with SF2, in canine tumor cell lines. Bacová et al (41) have demonstrated the potential of SCGE assay in prediction of intrinsic radiosensitivity using human ovarian carcinoma cell lines.…”