Protective role of electrophile-reactive glutathione for DNA damage repair inhibitory effect of dibromoacetonitrile
Yuko Ibuki , Yukako Komaki , Koki Suganuma , Carsten Prasse , Xin Yang , Chao Chen , Bin Xu , Xing-Fang Li
DOI:10.1016/j.jes.2022.05.015
Received March 15, 2022,Revised , Accepted May 06, 2022, Available online May 21, 2022
Volume 34,2022,Pages 305-314
Dibromoacetonitrile (DBAN) is a disinfection byproduct (DBP) and linked with cancer in rodents, but the mechanism of its carcinogenicity has not been fully elucidated. We recently reported that DBAN induced inhibition of nucleotide excision repair (NER). In this study, we investigated if glutathione (GSH) is involved in the DBAN-induced inhibition of NER. Human keratinocytes HaCaT were pretreated with L-buthionine-(S,R)-sulfoximine (BSO) to deplete intracellular GSH. BSO treatment markedly potentiated the DBAN-induced NER inhibition as well as intracellular oxidation. The recruitment of NER proteins (transcription factor IIH, and xeroderma pigmentosum complementation group G) to DNA damage sites was inhibited by DBAN, which was further exacerbated by BSO treatment. Our results suggest that intracellular GSH protects cells from DBAN-induced genotoxicity including inhibition of DNA damage repair.
