Radioresistance in mammals induced by low-level chronic irradiation: modeling and experimental investigations

Effects of chronic low-level preirradiation on radiosensitivity of mice is studied experimentally and by making use of the methods of mathematical modeling. The experiments show that a priming exposure to chronic internal irradiation can induce radioresistance in mice. The manifestation of this radioprotection effect is reduced mortality of preexposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic syndrome. Therefore, the theoretical investigation of the influence of preirradiation on radiosensitivity of mice is conducted by making use of the mathematical models that describe the dynamics of hematopoietic system in mice exposed to challenge acute irradiation following the chronic one. Modeling results show that the radioprotection effect of chronic low-level long-term (more than 1 mo) preirradiation on mice is caused by decreased radiosensitivity (radioresistance) of the granulocytopoietic system, which appeared at the level of one functional cell pool, blood granulocytes. In turn, the above-indicated state of radioresistance of the granulocytopoietic system is the consequence of hypercompensation of the radiation damage of this system resulting in relaxation to elevated concentrations of blood granulocytes and their nondividing and dividing bone-marrow precursors and in enhanced mitotic activity of the latter. Modeling results also indicate that the radiosensitization effect of chronic low-level short-term (less than 1 mo) preirradiation on mice is due to increased radiosensitivity of lymphopoietic, granulocytopoietic, and erythropoietic systems accompanied by increased or close to the normal level radiosensitivity of thrombocytopoietic system. In turn, increased radiosensitivity of above-noted hematopoietic lines is the consequence of an exhaustion of these cell systems. Modeling estimations of the duration of low-level chronic preexposures, which result in radioprotection and radiosensitization effects on mice, are in agreement with the relevant experimental data.