Sequential alteration of proto-oncogene expression in liver, spleen, kidney and brain of mice subjected to whole body irradiation.

Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the sequential alteration of proto-oncogene mRNA expression in liver, spleen, kidney and brain of mice after whole body irradiation (WBI). The mRNAs investigated in this study were Fas, c-fos, c-myc. bcl-2, and p53, and glyceraldehyde-3-phosphate dehydrogenase mRNA was employed as internal control. C3H/He mice aged 9-10 weeks were exposed to WBI of 7 Gy using a cobalt-60 teletherapy unit, without anesthesia, and sacrificed before and 0.1, 0.5, 1, 2, 3, 6, 12, 24, 48 and 96 h after irradiation. Their liver, spleen, kidney and brain were taken and immediately stored in liquid nitrogen until ready for RT-PCR. Each specimen was homogenized to extract RNA for conventional RT-PCR. The liver of mice administered 7 Gy of WBI revealed no significant changes in the expression of each of the mRNAs examined. In the spleen, c-fos mRNA expression decreased at 2 h following irradiation, and increased remarkably thereafter. In the kidney, no significant change in the expression of each mRNA was shown. In the brain c-fos mRNA expression decreased 1-24 h after irradiation, and showed a recovery thereafter. The remarkable differences in the sequential changes of c-fos mRNA expression following irradiation between each organ revealed by the present experiment may be an important aid in determining the tissue-specific radiosensitivity to ionizing radiation. Further investigations are, however, needed to clarify the signal transduction mechanisms which are mediated by the expression of these proto-oncogenes in each tissue following irradiation.