Involvement of MAPK signalling in radioadaptive response in BALB/c mice exposed to low dose ionizing radiation

Abstract

To investigate low dose ionizing radiation (LDIR)-induced adaptive response in lymphocytes of BALB/c mice and to elucidate related molecular mechanisms. Mice were exposed to a priming dose (PD) of 0.1 Gy and challenge dose (CD) of 2 Gy ionizing radiation. Proliferation response to mitogen concanavalin A was assessed using ³H thymidine incorporation and carboxyfluoresceinsuccinamidylester (CFSE) dye dilution. Early activation markers were assessed by flow cytometry, cytokines by ELISA, DNA damage by comet assay and mitogen activated protein kinase (MAPK) signaling by Western blotting. Radioadaptive response was observed in lymphocytes of mice exposed to PD prior to CD of ionizing radiation in terms of DNA damage, early activation markers CD69, CD71, cytokines IL-2, IFN-γ as well as proliferation. This effect was transient and observed 24 h after CD and not after 0 h or 72 h. Hyper activation of MAPK signaling pathways in lymphocytes from LDIR-exposed mice and abrogation by ERK and p38 inhibitors suggests the involvement of MAPK signaling in radioadaptive response. Our study demonstrates that LDIR-induced transient adaptive response was due to hyper activation of MAPK signaling. Our findings contribute towards the understanding of LDIR-induced adaptive response.

Keywords:

• Radioadaptive response
• BALB/c mice
• low dose ionizing radiation
• MAPK signaling
• ERK signalling

Acknowledgements

We express our sincere gratitude to Dr S. Chattopadhyay, Associate Director, BioScience Group, BARC for carefully going through the manuscript and giving constructive suggestions. We are extremely thankful to Dr Birajalaxmi Das for her support and inputs. We thank Mr N. S. Sidnalkar and Mr S. Shinde for their technical assistance.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.