Chk2 deficiency alleviates irradiation-induced taste dysfunction by inhibiting p53-dependent apoptosis.

Abstract

Taste dysfunction is one of the most common complications following radiotherapy, which leads to decreased appetite and life quality of patients suffering from head and neck cancer. The aim of this study was to investigate the role of checkpoint kinase 2 (Chk2) deficiency in irradiation-induced taste dysfunction. Alterations in oxidative stress, DNA damage, and potential signaling pathway were compared between Chk2-deficient (Chk2-/- ) mice and their wild-type (WT) littermates pre-irradiation and 7 and 30days postirradiation by biochemistry and immunohistochemistry. Chk2-/- mice showed less loss of type II and type III taste cells, lower expression of p53, caspase-3, and cleaved caspase-3, and lower apoptosis levels. However, no significant differences in H2 O2 and MDA concentrations, T-SOD and GSH-Px activities, and expression of SOD1, SOD2, and 8-OHdG were detected in the taste buds of Chk2-/- mice as compared to those of WT mice. Chk2 deficiency downregulated the expression of p53 and inhibited cellular apoptosis, partly contributing to the radioprotective effect on taste cells, but did not alter oxidative stress levels, antioxidant ability, and oxidative DNA damage in taste buds.