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 o...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 Ha Ca T 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.展开更多
基金supported by the Kurita Water and Environment Foundation (No. 18E030)JSPS KAKENHI Grant Number 19K15793。
文摘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 Ha Ca T 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.
