Involvement of MAPK signalling in radio-adaptive response in BALB/c mice

Radio-adaptive response (RAR) is a phenomenon in which exposure to a sublethal dose of ionizing radiation, known as priming dose (PD), leads to increased resistance to the damage by a subsequent higher dose exposure, known as the challenge dose (CD). Immune system is one of the important cell renewal systems and is, therefore, ideal for studying RAR. We studied radiation-induced immunosuppression in splenic lymphocytes as the endpoint for RAR. BALB/c mice were irradiated with 0.1 Gy (PD) and 2 Gy (CD), and priming dose and challenge dose with an interval of 4 hour (P+CD). Experiments were carried out after 24 hours of CD exposure, and the ability to abrogate the CD-induced immunosuppression was assessed as a measure of RAR. Splenic lymphocytes from mice exposed to P+CD showed increased proliferation responses to mitogen Con A as compared to those isolated from mice irradiated with CD alone. Adaptive response was seen in terms of expression of early activation markers, like CD69, CD71, cytokines IL 2, IFN g as well as 3H thymidine incorporation. This adaptive response observed at 24 hours was associated with increased expression of MAPK-signalling pathways. Abrogation of low dose-induced adaptive response by specific inhibitors further confirms the involvement of MAPK signalling. Our study demonstrates that low dose-induced transient activation of MAPK-signalling pathways is responsible for increased proliferation responses after low dose radiation. (author)