The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

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http://dx.doi.org/10.7868/s0869803113020148DOI Listing

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