Exploration of Indole Compounds as Candidate for Radiation Mitigators

Abstract

In this study, to develop radiomitigators capable of the emergency medical care of patients involved in radiation accidents, we investigated the radiomitigative effects and their underlying mechanisms of indole compounds such as DIM, GRM, and INM. The human normal fibroblast cell line, MRC-5 cells were administered 0.1% DMSO or each indole compound at 10 µM within 50-60 minutes after X-irradiated with 0-4 Gy. Next, we evaluated the alteration in the number of alive cells, clonogenic potential, DNA double-strand breaks, DNA damage repair activities, and protein expression related to regulate the oxidative stress response. Our results showed that DIM treatment suppressed radiation-induced decrease in the number of alive cells and clonogenic potential. Then, DIM treatment significantly decreased DNA double-strand breaks and highly increased Nrf2 via increased phospho-GSK-3β (Ser9) expression. These findings suggest that, in part, increased expression of p-GSK-3β (Ser9) by DIM treatment reduced DNA double-strand breaks via activation of Nrf2, resulting mitigated radiation-induced a decrease in the number of alive cells and clonogenic potential. Therefore, DIM, not GRM and INM, is a potential candidate for radiomitigators that can be applied to the radiation emergency medicine.