DOI: 10.6084/m9.figshare.20161532.v1
title: Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice

description: Radiation triggers cell death events through signaling proteins, but the combined mechanism of these events is unexplored The Wnt canonical pathway, on the other hand, is essential for cell regeneration and cell fate determination. The relationship between the Wnt pathway's response to radiation and its role in radiotoxicity is overlooked, despite the fact that it is a critical molecular control of the cell. The Wnt pathway has been predicted to have radioprotective properties in some reports, but the overall mechanism is unknown. We intend to investigate how this combined cascade works throughout the radiation process and its significance over radiotoxicity. 30 adult mice were irradiated with electron beam radiation, and 5 served as controls. Mice were sacrificed after 24 hours and 30 days of irradiation. We assessed DNA damage studies, oxidative stress parameters, mRNA profiles, protein level (liver, kidney, spleen, and germ cells), sperm viability, and motility. Observation: The mRNA profile helps to understand how the combined cascade of Wnt pathway and NHEJ work together during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all cases, particularly in germ cells. Recuperation was likewise seen in post 30 day’s radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes that reproductive physiology is exceptionally sensitive to radiation, even at the molecular level. It also suggests the suppression of Lef1/Axin2 could be the main reason for permanent failure of the sperm function process. Post irradiation likewise influences the morphology of sperm. The decrease in mRNA levels of Lef1, Axin2, Survivin, Ku70 and XRCC6 level suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanisms in a coupled manner. An increase in Bax, Bcl2 and caspase3 suggests apoptosis activation followed by the decreased expression of enzymatic-antioxidants. Controlled several interlinked such as the Wnt canonical pathway, NHEJ pathway and intrinsic apoptotic pathway execute when whole body expose to radiation. These pathways decide the cell fate whether it will survive or will go to apoptosis which may further be used in a study to counterpart and better comprehend medication focus on radiation treatment (1)Electron beam radiation penetrate inside the cell leading to production of free radicals (2) which further produce ROS, RNS and lipid peroxidation. (3) To counteract with ROS and RNS, SOD, Cat and iNOS produce to scavenge free radicals. (4) Wnt3a, a natural activator of Wnt canonical pathway binds to Fz receptor and start Wnt canonical pathway for cell proliferation and survival from radiation. (1) Electron beam radiation also cause DSB which further activate (5) NHEJ pathway for DNA repair. (1) Electron beam initiate the intrinsic apoptotic pathway (6) which lead to cell death. Survivin a candidate molecule of (4)Wnt canonical pathway inhibit the action of intrinsic apoptotic pathway by inhibiting caspase 3 which rescue cell from apoptosis.