Pinhua Zhang , Yunyun Wu , Chunnan Piao , Yanchao Song , Yanfang Zhao , Yumin Lyu , Quanfu Sun , Jianxiang Liu
{"title":"高水平氡暴露诱发非铀矿工全基因组DNA甲基化的变化。","authors":"Pinhua Zhang , Yunyun Wu , Chunnan Piao , Yanchao Song , Yanfang Zhao , Yumin Lyu , Quanfu Sun , Jianxiang Liu","doi":"10.1016/j.mrgentox.2023.503683","DOIUrl":null,"url":null,"abstract":"<div><p>In China, according to statistics about underground non-uranium mine radon levels, 15% exceed the national standard intervention level of 1000 Bq/m<sup>3</sup>, and some mines may exceed 10,000 Bq/m<sup>3</sup>. The relationship between radon exposure in underground miners and lung cancer has already been established, but the mechanisms and biological processes underlying it are poorly understood. In order to identify the genome-wide DNA methylation profile associated with long-term radon exposure, we performed the Infinium Human Methylation 850 K BeadChip measurement in whole blood samples obtained from 15 underground non-uranium miners and 10 matched aboveground control workers. Radon concentrations in the air of workplaces and living environments were measured by CR-39 radon detectors, and annual effective doses were calculated using the detection data. Under the high radon concentration with an average value of 12,700 Bq·m<sup>−3</sup>, a total of 165 significant differentially methylated positions (127 hypermethylated sites and 38 hypomethylated sites) annotated to 71 genes were identified in underground miners (|Δ<em>β</em>| ≥ 0.10, <em>p</em> < 0.05), and the average DNA methylation level of 165 DMPs was significantly higher than that of the control workers. Most DMPs were found on chromosome 1, and approximately one-quarter of them were located in genomic promoter regions. Through bioinformatics analysis and pyrosequencing validation, five candidate genes differentially methylated by radon, including <em>TIMP2</em>, <em>EMP2</em>, <em>CPT1B</em>, <em>AMD1</em> and <em>SLC43A2</em> were identified. GO and KEGG analysis implicated that long term radon exposure could induce the lung cancer related biological processes such as cell adhesion and cellular polarity maintenance. Our study provides evidence for the alterations of genome-wide DNA methylation profiles induced by long-term high level radon exposure, and new insights into searching for carcinogenic biomarkers of high radon exposure in future studies.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503683"},"PeriodicalIF":2.3000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alteration of genome-wide DNA methylation in non-uranium miners induced by high level radon exposure\",\"authors\":\"Pinhua Zhang , Yunyun Wu , Chunnan Piao , Yanchao Song , Yanfang Zhao , Yumin Lyu , Quanfu Sun , Jianxiang Liu\",\"doi\":\"10.1016/j.mrgentox.2023.503683\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In China, according to statistics about underground non-uranium mine radon levels, 15% exceed the national standard intervention level of 1000 Bq/m<sup>3</sup>, and some mines may exceed 10,000 Bq/m<sup>3</sup>. The relationship between radon exposure in underground miners and lung cancer has already been established, but the mechanisms and biological processes underlying it are poorly understood. In order to identify the genome-wide DNA methylation profile associated with long-term radon exposure, we performed the Infinium Human Methylation 850 K BeadChip measurement in whole blood samples obtained from 15 underground non-uranium miners and 10 matched aboveground control workers. Radon concentrations in the air of workplaces and living environments were measured by CR-39 radon detectors, and annual effective doses were calculated using the detection data. Under the high radon concentration with an average value of 12,700 Bq·m<sup>−3</sup>, a total of 165 significant differentially methylated positions (127 hypermethylated sites and 38 hypomethylated sites) annotated to 71 genes were identified in underground miners (|Δ<em>β</em>| ≥ 0.10, <em>p</em> < 0.05), and the average DNA methylation level of 165 DMPs was significantly higher than that of the control workers. Most DMPs were found on chromosome 1, and approximately one-quarter of them were located in genomic promoter regions. Through bioinformatics analysis and pyrosequencing validation, five candidate genes differentially methylated by radon, including <em>TIMP2</em>, <em>EMP2</em>, <em>CPT1B</em>, <em>AMD1</em> and <em>SLC43A2</em> were identified. GO and KEGG analysis implicated that long term radon exposure could induce the lung cancer related biological processes such as cell adhesion and cellular polarity maintenance. Our study provides evidence for the alterations of genome-wide DNA methylation profiles induced by long-term high level radon exposure, and new insights into searching for carcinogenic biomarkers of high radon exposure in future studies.</p></div>\",\"PeriodicalId\":18799,\"journal\":{\"name\":\"Mutation research. Genetic toxicology and environmental mutagenesis\",\"volume\":\"891 \",\"pages\":\"Article 503683\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutation research. 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Alteration of genome-wide DNA methylation in non-uranium miners induced by high level radon exposure
In China, according to statistics about underground non-uranium mine radon levels, 15% exceed the national standard intervention level of 1000 Bq/m3, and some mines may exceed 10,000 Bq/m3. The relationship between radon exposure in underground miners and lung cancer has already been established, but the mechanisms and biological processes underlying it are poorly understood. In order to identify the genome-wide DNA methylation profile associated with long-term radon exposure, we performed the Infinium Human Methylation 850 K BeadChip measurement in whole blood samples obtained from 15 underground non-uranium miners and 10 matched aboveground control workers. Radon concentrations in the air of workplaces and living environments were measured by CR-39 radon detectors, and annual effective doses were calculated using the detection data. Under the high radon concentration with an average value of 12,700 Bq·m−3, a total of 165 significant differentially methylated positions (127 hypermethylated sites and 38 hypomethylated sites) annotated to 71 genes were identified in underground miners (|Δβ| ≥ 0.10, p < 0.05), and the average DNA methylation level of 165 DMPs was significantly higher than that of the control workers. Most DMPs were found on chromosome 1, and approximately one-quarter of them were located in genomic promoter regions. Through bioinformatics analysis and pyrosequencing validation, five candidate genes differentially methylated by radon, including TIMP2, EMP2, CPT1B, AMD1 and SLC43A2 were identified. GO and KEGG analysis implicated that long term radon exposure could induce the lung cancer related biological processes such as cell adhesion and cellular polarity maintenance. Our study provides evidence for the alterations of genome-wide DNA methylation profiles induced by long-term high level radon exposure, and new insights into searching for carcinogenic biomarkers of high radon exposure in future studies.
期刊介绍：
Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas:
New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results).
Alternatives to and refinement of the use of animals in genotoxicity testing.
Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials.
Studies of epigenetic changes in relation to genotoxic effects.
The use of structure-activity relationships in predicting genotoxic effects.
The isolation and chemical characterization of novel environmental mutagens.
The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures.
The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing).
MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.
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