Blood Sample May Establish Patient Radiosensitivity

A new study suggests that flow cytometry analysis can be used to measure a patient’s DNA sensitivity to radiation and chemotherapy treatments.

Under development at Sahlgrenska Academy (Göteborg, Sweden), the flow-cytometry-based cell division (CD) assay uses the thymidine analogue 5-ethynyl-2’-deoxyuridine (EdU) to measure the proliferative ability of cells after DNA damaging treatment. In validation studies, the CD assay measured sensitivity to radiation of human skin fibroblasts with a correlation similar to standard clonogenic survival assay, and in a relatively short time frame. Using easily sampled peripheral blood lymphocytes, the CD assay was able to identify variation in intrinsic sensitivity to radiation, and also detected increased sensitivity in patients with DNA repair defects.

As exposure to ionizing radiation generates free radicals that carry out most part of the toxic effects, the researchers conducted a second study to examine if pretreating cells with an Nrf2 transcription factor activator, which regulates the cellular antioxidant system, could influence sensitivity to radiation. The results showed that repeated pretreatment of cells with Nrf2 activators, isothiocyanate sulforaphane, or synthetic triterpenoid bardoxolone methyl can enhance cytoprotection. The study was presented as a PhD dissertation in September 2017.

“The main idea behind our method is to measure patient sensitivity during the planning process for the cancer treatment and to identify which patients are extremely sensitive,” study dissertation presenter Sherin Mathew, PhD. “It will be better to have this knowledge about the patients; as it stands right now we don't know how each patient will respond when the radiation or chemotherapy is administered. The idea is that it will be possible to test sensitivity and prevent extremely sensitive patients from having serious side effects.”

Flow cytometry is a biophysical technology employed in cell counting, cell sorting, biomarker detection, and protein engineering by suspending cells in a stream of fluid and passing them through an electronic laser or impedance-based detection apparatus that allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second. Flow cytometry is routinely used in the diagnosis of health disorders, especially blood cancers, but has other applications in basic research, clinical practice, and clinical trials.

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