Evaluation of Apoptosis in the Normal Rat Brain after Intraoperative Irradiation

ABSTRACT

Radiation therapy is one of the most important treatment modalities following surgery of the primary malignant or metastatic brain tumors. But radiation can be harmful to normal healthy brain tissues around the tumor. There have been numerous reports of radiation induced damage such as delayed necrosis to human brain after therapeutic exposure. Apoptosis is a form of cell death with morphological and biochemical features that differ from those of necrosis. The aim of this study is to evaluate the apoptosis in normal rat brain after irradiation. Twenty one Sprague-Dawley rats were given a single dose of 10 Gy using high dose rate Ir-192 over 5 minutes at the right frontal region. Apoptosis was evaluated by the TUNEL method(In-situ end labelling technique) and mutant p53 protein, bc1-2 and bax genes were evaluated by immunohistochemical stain. Apoptosis was assessed at 1 week(group A, n=5), 2 week(group B, n=), 4 week(group C, n=), 6 week(group D, n=), 8 week(group E, n=) after irradiation. Apoptosis was noted with 20% of cases(1/5) in group A, 40% of cases(2/5) in group B, 60% of cases(3/5) in group C, 67% of cases(2/3) in group D and 100% of cases(3/3) in group E. Overall apoptosis positive rate was 52.4%(11/21). Apoptosis was most prominently found in external granular and external pyramidal layer(82%, 9/11) and found one case in internal pyramidal layer and the other one case in corticowhite matter junction. There were no positive stainning for mutant p53 protein, bc1-2 and bax gene in all cases pertaining to the phenomenon of apoptosis. In conclusion, apoptosis was evident in the rat brain after irradiation and the incidence of apoptosis was increased with time after irradiation. But the genes related to apoptosis after irradiation were not apparent in this study. Further evaluation including biochemical and clonogenic study needs to clarify the mechanism of apoptosis in normal brain after irradiation.