Molecular analysis of the involvement of protein kinase C in radioadaptive response

Radioadaptive response is a biological defense mechanism that is induced by low-dose ionizing irradiation for cellular resistance to the genotoxic effects of subsequent irradiation. We have suggested that the radioadaptive response is mediated through the pathways involving protein kinase C (PKC) alpha and p38 mitogen-activated protein kinase. However, the molecular role of PKC is still largely elusive. Here, we examined the involvement of PKCα in radioadaptive response by the use of RNAi. We introduced three kinds of siRNA into m5S cells, each of which targets different site of the mouse PKC α gene, Prkca. Two of three siRNAs greatly reduced the amount of Prkca mRNA, indicating that RNAi is effective for suppressing the expression of the Prkca gene. We examined the radioadaptive response in the m5S cells in which the Prkca mRNA was suppressed. Cells were pre-treated with low concentration of hydrogen peroxide followed by irradiation with 5 Gy X-rays, and analyzed the induction of MN. The radioadaptive response was suppressed in the cells with low amount of the Prkca mRNA. These results indicate that PKC alpha is one of the critical factors of the signal transduction pathway in the radioadaptive response. (author)