Abstract
Development of novel approaches linking the physical characteristics of particles with biological responses are of high relevance for the field of particle therapy. In radiobiology, the clonogenic survival of cells is considered the gold standard assay for the assessment of cellular sensitivity to ionizing radiation. Toward further development of next generation biodosimeters in particle therapy, cell-fluorescent ion track hybrid detector (Cell-FIT-HD) was recently engineered by our group and successfully employed to study physical particle track information in correlation with irradiation-induced DNA damage in cell nuclei. In this work, we investigated the feasibility of Cell-FIT-HD as a tool to study the effects of clinical beams on cellular clonogenic survival. Tumor cells were grown on the fluorescent nuclear track detector as cell culture, mimicking the standard procedures for clonogenic assay. Cell-FIT-HD was used to detect the spatial distribution of particle tracks within colony-initiating cells. The physical data were associated with radiation-induced foci as surrogates for DNA double-strand breaks, the hallmark of radiation-induced cell lethality. Long-term cell fate was monitored to determine the ability of cells to form colonies. We report the first successful detection of particle traversal within colony-initiating cells at subcellular resolution using Cell-FIT-HD.
Highlights
Radiotherapy with protons and heavier ions has become a swiftly growing field, and it is becoming an integrative part of therapy of solid tumors, due to its high success rate in treating certain tumors [1]
Colony formation assay is a quantitative, macroscopic assay, which represents the standard for studying cell’s sensitivity to irradiation [8]. It provides valuable information on the outcome of a large cell population upon the irradiation. This assay does not provide an insight on a single cell fate within a population, and why certain cells within a population will stop dividing and eventually die, whereas the other ones will still be capable of clonogenic growth
It can be hypothesized that certain cells within a population accumulate lethal level of irradiation-induced damage, and lose capability to divide and form colonies, whereas the other cells remain unaffected
Summary
Radiotherapy with protons and heavier ions has become a swiftly growing field, and it is becoming an integrative part of therapy of solid tumors, due to its high success rate in treating certain tumors [1]. A cell-fluorescent ion track hybrid detector (CellFIT-HD) was engineered by our group. It provides information on spatial correlation between single ion traversals and the events within a cell [2, 3]. Cell-FIT-HD technology is based on growing a cellular monolayer (biological compartment) on a surface of a fluorescent nuclear track detector [FNTD; physical compartment [4]]. Due to its unique design, Cell-FIT-HD enables simultaneous investigation of microscopic beam parameters and their effect on various cellular structures and biological processes, using confocal laser scanning microscope [5]
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