Suppression of p53 and Bax accumulation after X-irradiation by small dose preirradiation in radioadaptive survival response of C57BL/6 mice

It has been reported by the authors that X-irradiation with 0.30-0.50 Gy two weeks before a second exposure to a midlethal dose significantly reduced the bone marrow death rate in ICR and C57BL/6 strains of mice. Though radioadaptive response within blood-forming tissues has been speculated on the induction the radioresistance, molecular mechanism has been unknown yet. The present study was carried out to elucidate molecular mechanisms for the radioadaptive survival response. Effect of preirradiation (0.45 Gy) on p53 as well as Bax accumulation after challenging irradiation was studied in C57BL/6N mice. Accumulation of p53 was examined by the Western blotting method in the brain, thymus, lung, liver, intestine, spleen and bone-marrow of mice collected 5 hrs after challenging irradiation with 3 Gy. The challenging irradiation increased p53. The priming irradiation itself did not show any change in p53 level 2 weeks later. p53 accumulation after challenging irradiation with 3 Gy was significantly suppressed by the preirradiation in the spleen, among the tissues examined. Suppression of p53 by preirradiation in the present study in mice is similar to our previous finding in cultured cell system. Histological study showed that the preirradiation suppressed both p53 and Bax accumulation in the spleen 7 days after challenging irradiation with 3 Gy. From these results, the preirradiation seems to decrease apoptosis after challenging high-dose irradiation, which would be induced by p53 and Bax signal transduction. Decreased apoptosis would result in an increase in cell survival of the spleen, a hematopoietic tissue. This might favor recovery from radiation-induced acute hematopoietic injury, and finally increased survival rate. This situation seems to be induced through apoptosis of highly radiation-sensitive cells after the priming irradiation that leaves resistant cells: the radiation-sensitive cells would be replaced during the interval time by radiation-resistant cells after cell division of the surviving resistant cells. (author)