Establishment of a new laboratory test for radiation sensitivity targeting p53 signal transduction system

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Although radiation therapy is one of the effective therapies for cancers, there are some patients who are extraordinarily sensitive to radiation in whom radiation-induced skin ulcer and perforation of gastro-intestinal tracts sometimes occur. Since there is no way to identify such radiation hypersensitive patients before therapy, we tried to establish a laboratory test for this purpose in the present study. Objects are mamma cancer patients who are planned to receive radiation therapy. Peripheral blood mononuclear cells were obtained from these patients before and after radiation. Radiation-induced skin damage was evaluated in all patients, but there was no significant difference among patients, indicating that radiation hypersensitive patients were not included in the study. Absolute peripheral blood lymphocyte count decreased in all patients after radiation, but absolute neutrophil count showed no changes. Interestingly, radiation sensitivity was different among lymphocyte subsets, and T lymphocytes were more sensitive than B lymphocyte or NK lymphocytes. CD8+ T-cell subset was the most sensitive lymphocytes and decrease of the absolute count prolonged even after 12 weeks after radiation. Nevertheless, increase of apoptotic lymphocytes was not observed in the peripheral blood. We then quantified mRNAs of various molecules that are supposed to be influenced by radiation, such as p53, p14ARF、p16INK4A and Hzf. There was however no significant correlation between the changes of the mRNA levels of these molecules and the level of the decrease of absolute lymphocyte counts.