Effects of H19/SAHH/DNMT1 on the Oxidative DNA Damage Related to Benzo[a]Pyrene Exposure

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 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), 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 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.

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Effects of H19/SAHH/DNMT1 on the oxidative DNA damage related to Benzo[a]pyrene exposure

10.21203/rs.3.rs-944681/v1 ◽

2021 ◽

Author(s):

Ye Fu ◽

Xuejing Li ◽

Baolong Pan ◽

Yingying Niu ◽

Bin Zhang ◽

...

Keyword(s):

Dna Damage ◽

Noncoding Rna ◽

Dna Methyltransferase ◽

Oxidative Dna Damage ◽

Coke Oven ◽

Dna Methyltransferase 1 ◽

Adenosylhomocysteine Hydrolase ◽

Cycle Arrest ◽

Phase Arrest ◽

Coke Oven Workers

Abstract Background: 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 PAHs remain unclear. Results: 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 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. Conclusions: A H19/SAHH/DNMT1 axis was involved in OGG1 methylation, oxidative DNA damage and cell cycle arrest by carcinogen BaP.

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Mixture Analysis of Associations between Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Sperm Oxidative DNA Damage

Annals of Work Exposures and Health ◽

10.1093/annweh/wxab072 ◽

2021 ◽

Author(s):

Hueiwang Anna Jeng ◽

Sinjini Sikdar ◽

Chih-Hong Pan ◽

Guo-Ping Chang-Chien

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Oxidative Damage ◽

Oxidative Dna Damage ◽

Selection Process ◽

Coke Oven ◽

Breathing Zone ◽

Suggestive Association ◽

Polycyclic Aromatic ◽

Coke Oven Workers

Abstract Objective This study aimed to determine (i) associations between levels of the polycyclic aromatic hydrocarbon (PAH) mixture with 16 targeted PAH compounds in the personal breathing zone area and sperm oxidative DNA damage, (ii) associations between levels of individual PAH compounds and sperm oxidative DNA damage, (iii) oxidative stress as the mode of action for the genotoxic effects on sperm, and (iv) any dose–response relationship between exposure to the PAH mixture and/or individual PAH compounds and sperm oxidative DNA damage. Methods Sixteen targeted PAH compounds in the personal breathing zone area of 38 coke-oven workers and 24 control subjects were quantified using gas chromatography–mass spectrometry. Sperm oxidative damage and status were evaluated by measuring levels of sperm 7,8-dihydro-8-oxoguanie (8-oxodGuo), seminal malondialdehyde (MDA) and seminal reactive oxygen species (ROS). Bayesian kernel machine regression with hierarchical variable selection process was employed to determine associations of the PAH mixture and the biomarkers of sperm oxidative damage. A novel grouping approach needed for the hierarchical variable selection process was developed based on PAH bay region and molecular weight. Results The PAH mixture exhibited a positive trend with increased sperm 8-oxodGuo levels at their lower percentiles (25th–50th). The exposure of the PAH mixture was associated with increased MDA levels in sperm. Bay and bay-like regions of the PAH mixture were the most important group for estimating the associations between the PAH mixture and sperm oxidative stress status. Benzo[a]anthracene was the main individual PAH compound that was associated with increased MDA levels. Conclusion Sperm oxidative DNA damage induced by occupational exposure to the PAH mixture had a suggestive association with increased MDA levels in coke-oven workers. Finally, the study identified that the individual PAH compound, benzo[a]anthracene, was the primary driver for the suggestive association between the PAH mixture and sperm oxidative damage.

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CYP1A1 methylation mediates the effect of smoking and occupational polycyclic aromatic hydrocarbons co-exposure on oxidative DNA damage among Chinese coke-oven workers

Environmental Health ◽

10.1186/s12940-019-0508-0 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 4

Author(s):

Yanli Liu ◽

Xuejing Li ◽

Bin Zhang ◽

Ye Fu ◽

Aimin Yang ◽

...

Keyword(s):

Dna Damage ◽

Polycyclic Aromatic Hydrocarbons ◽

Aromatic Hydrocarbons ◽

Oxidative Dna Damage ◽

Coke Oven ◽

Polycyclic Aromatic ◽

Coke Oven Workers

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OGG1 methylation mediated the effects of cell cycle and oxidative DNA damage related to PAHs exposure in Chinese coke oven workers

Chemosphere ◽

10.1016/j.chemosphere.2019.02.114 ◽

2019 ◽

Vol 224 ◽

pp. 48-57 ◽

Cited By ~ 4

Author(s):

Ye Fu ◽

Yingying Niu ◽

Baolong Pan ◽

Yanli Liu ◽

Bin Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Coke Oven ◽

Coke Oven Workers

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Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Their Interactions with the Environment: Influences on Oxidative DNA Damage and Lipid Peroxidation in Coke Oven Workers

Environmental Science & Technology ◽

10.1021/es4055516 ◽

2014 ◽

Vol 48 (7) ◽

pp. 4120-4128 ◽

Cited By ~ 17

Author(s):

Qifei Deng ◽

Xiayun Dai ◽

Huan Guo ◽

Suli Huang ◽

Dan Kuang ◽

...

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Polycyclic Aromatic Hydrocarbons ◽

Aromatic Hydrocarbons ◽

Oxidative Dna Damage ◽

Coke Oven ◽

Polycyclic Aromatic ◽

Coke Oven Workers

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Mollugin induced oxidative DNA damage via up-regulating ROS that caused cell cycle arrest in hepatoma cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2022.109805 ◽

2022 ◽

pp. 109805

Author(s):

Xin-ge Ke ◽

Yi-yi Xiong ◽

Bing Yu ◽

Chong Yuan ◽

Peng-yu Chen ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Oxidative Dna Damage ◽

Hepatoma Cells ◽

Cycle Arrest

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Abstract A18: Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage

10.1158/1538-7445.chromepi15-a18 ◽

2016 ◽

Author(s):

Ning Ding ◽

Emily M. Bonham ◽

Brooke E. Hannon ◽

Stephen B. Baylin ◽

Heather M. O'Hagan

Keyword(s):

Dna Damage ◽

Mismatch Repair ◽

Dna Methyltransferase ◽

Oxidative Dna Damage ◽

Dna Methyltransferase 1 ◽

Mismatch Repair Proteins ◽

Methyltransferase 1

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Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase

Cells ◽

10.3390/cells9010225 ◽

2020 ◽

Vol 9 (1) ◽

pp. 225 ◽

Cited By ~ 2

Author(s):

Zhongliang Jiang ◽

Yanhao Lai ◽

Jill M. Beaver ◽

Pawlos S. Tsegay ◽

Ming-Lang Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Dna Damage ◽

Dna Polymerase ◽

Dna Methyltransferase ◽

Oxidative Dna Damage ◽

De Novo ◽

Brca1 Gene ◽

Methylation Pattern ◽

Dna Polymerase Β

DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from −189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase β (pol β). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol β and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.

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