期刊
CARCINOGENESIS
卷 43, 期 1, 页码 52-59出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgab087
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资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [19H04273]
- Central Research Institute of Fukuoka University [197003]
- Grants-in-Aid for Scientific Research [19H04273] Funding Source: KAKEN
The study demonstrates that acetaldehyde-induced DNA lesions can be repaired through the nucleotide excision repair (NER) mechanism, while also generating reversible GG crosslinks. Experimental evidence suggests that DNA polymerase eta may induce G to T transversions in acetaldehyde-treated DNA.
Nucleotide excision repair (NER) is a repair mechanism that removes DNA lesions induced by UV radiation, environmental mutagens and carcinogens. There exists sufficient evidence against acetaldehyde suggesting it to cause a variety of DNA lesions and be carcinogenic to humans. Previously, we found that acetaldehyde induces reversible intra-strand GG crosslinks in DNA similar to those induced by cis-diammineplatinum(II) that is subsequently repaired by NER. In this study, we analysed the repairability by NER mechanism and the mutagenesis of acetaldehyde. In an in vitro reaction setup with NER-proficient and NER-deficient xeroderma pigmentosum group A (XPA) cell extracts, NER reactions were observed in the presence of XPA recombinant proteins in acetaldehyde-treated plasmids. Using an in vivo assay with living XPA cells and XPA-correcting XPA cells, the repair reactions were also observed. Additionally, it was observed that DNA polymerase eta inserted dATP opposite guanine in acetaldehyde-treated oligonucleotides, suggesting that acetaldehyde-induced GG-to-TT transversions. These findings show that acetaldehyde induces NER repairable mutagenic DNA lesions. Previously, we found that acetaldehyde induces reversible intra-strand GG crosslinks that are fragile under general experimental conditions. Here, we show that NER repaired acetaldehyde-treated DNAs in vitro and in vivo and translesion-type DNA polymerase eta induced G to T transversion.
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