The major goal of radiotherapy is to destroy cancer cells in the treated area, which can cure or reduce the probability of cancer recurrence. However, radiotherapy usually damage normal tissue surrounding the tumor. Different types of such side effects of radiotherapy are called early/acute and late irradiation injury reactions. Differential responses of tumor and normal tissue that favor the latter one is an obvious prerequisite for an effective radiation treatment strategy. Consequently, clinical research trials are planned to identify better protocols of radiotherapy: to maximize damage to cancer tissue and to minimize effect of radiation to normal tissue. Selecting patients for specific radiotherapy strategy (therapy individualization) would be greatly facilitated if reliable makers of radio-resistance/radio-sensitivity were available in clinical practice.

Here we aimed to asses whether cytogenetic tests of radiosensitivity in vitro could be used to predict the response of individual patients to radiotherapy. As an experimental model we have used lymphocytes isolated from blood of patients with neck and head cancer (samples were collected before the start of radiotherapy). Lymphocytes isolated form a group of 60 patients were analyzed, as well as lymphocytes isolated from blood of 30 healthy donors. The single-cell gel electrophoresis (comet assay) has been used to quantify a background level of DNA damage and kinetics of DNA repair after in vitro irradiation with a 2Gy dose. The micronucleus test has been used to analyze residual DNA damage that is not repaired after in vitro irradiation with 2Gy or 4Gy doses.

Using the comet assay we have identified three group of patients with low, medium and high level of the background DNA damage (1-20, 20-100 and >100 a.u., respectively). The nuclear division index (NDI) established by the micronucleus test was 1.35 to 3.78 after 2Gy dose and 1.07 to 3.17 after 4Gy dose. Interestingly, the ratio of micronuclei to binuclear cells has been higher after 2Gy dose, yet the ratio of micronuclei to all cells ratio has been higher after 4Gy dose. Importantly, the NDI of lymphocytes estimated after a 4Gy dose has correlated with the level of the acute injury reaction after radiotherapy. In addition, low rate of DNA repair in lymphocytes irradiated in vitro (analyzed by comet assay) correlated with faster appearance of maximum injury reaction in vivo.

The project was supported by the Ministry of Science and Higher Education, grant 2P05B12630.

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