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- Title
Effects of H19/SAHH/DNMT1 on the oxidative DNA damage related to benzo[a]pyrene exposure.
- Authors
Fu, Ye; Li, Xuejing; Pan, Baolong; Niu, Yingying; Zhang, Bin; Zhao, Xinyu; Nie, Jisheng; Yang, Jin
- Abstract
The mechanisms that long noncoding RNA (lncRNA) H19 binding to S-adenosylhomocysteine hydrolase (SAHH) interacted with DNA methyltransferase 1 (DNMT1) and then regulated DNA damage caused by polycyclic aromatic hydrocarbons (PAHs) remain unclear. A total of 146 occupational workers in a Chinese coke-oven plant in 2014 were included in the final analyses. We used high-performance liquid chromatography mass spectrometry (HPLC–MS) equipped to detect urine biomarkers of PAHs exposure, including 2-hydroxynaphthalene (2-NAP), 2-hydroxyfluorene (2-FLU), 9-hydroxyphenanthrene (9-PHE) and 1-hydroxypyrene (1-OHP). The levels of SAM and SAH in plasma were detected by HPLC-ultraviolet. By constructing various BEAS-2B cell models exposed to 16 μM benzo[a]pyrene (BaP) for 24 h, toxicological parameters reflecting distinct mechanisms were evaluated. We documented that urinary 1-hydroxypyrene (1-OHP) levels were positively associated with blood H19 RNA expression (OR: 1.51, 95% CI: 1.03–2.19), but opposite to plasma SAHH activity (OR: 0.63, 95% CI: 0.41–0.98) in coke oven workers. Moreover, by constructing various BEAS-2B cell models exposed to benzo[a]pyrene (BaP), we investigated that H19 binding to SAHH exaggerated DNMT1 expressions and activity. Suppression of H19 enhanced the interaction of SAHH and DNMT1 in BaP-treated cells, decreased eight-oxoguanine DNA glycosylase 1 (OGG1) methylation, reduced oxidative DNA damage and lessened S phase arrest. However, SAHH or DNMT1 single knockdown and SAHH/DNMT1 double knockdown showed the opposite trend. A H19/SAHH/DNMT1 axis was involved in OGG1 methylation, oxidative DNA damage and cell cycle arrest by carcinogen BaP.
- Subjects
BENZOPYRENE; LIQUID chromatography-mass spectrometry; DNA damage; GENE expression; DNA adducts; PYRENE; LINCRNA; POLYCYCLIC aromatic hydrocarbons
- Publication
Environmental Science & Pollution Research, 2023, Vol 30, Issue 5, p11706
- ISSN
0944-1344
- Publication type
Article
- DOI
10.1007/s11356-022-22936-7