Ionizing radiation induces DNA damage, which generates a complex array of genotoxic responses. These responses depend on the type of DNA damage, which in turn can lead to unique cellular responses. High LET radiation results in clustered damages.This evokes specific signaling responses, which can be cytotoxic or cytoprotective in nature. In the present study the effect of carbon ion irradiation on p44/42 MAPK and NF_-κ B, which are essentially survival factors, have been studied. Moreover,the effect of inhibition of DNA-PK, which is an important component of DNA repair mechanism, with wortmanin on these signaling factors has been studied. The expression of p44/42 MAPK was different at 0.1 Gy and 1 Gy and wortmanin was found to inhibit its expression. NF_-κBe xpression was higher at 1 Gy than at 0.1 Gy and its expression is unaffected by inhibition of DNA-PK. The notable findings of this study are that the responses to high and low dose of high LET radiation are essentially different and th e6h time point post irradiation is crucial in deciding the response and needs further investigation.