期刊论文详细信息
Medicina
Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
Wei Wang1  Shuyin Duan1  Xiaoshan Zhou1  Songcheng Yu2  Xiaoling Wei3  Feifei Feng3  Yongjun Wu3  Huijie Yuan3  Lingbo Qu4 
[1] Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China;Department of Sanitary Chemistry, College of Public Health, Zhengzhou University, Zhengzhou 450001, China;Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China;Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou University, Zhengzhou 450001, China;
关键词: coal tar pitch extract;    BEAS-2B cells;    epigenetics;    DNA methylation;    occupational lung cancer;    biomarkers;   
DOI  :  10.3390/medicina57010024
来源: DOAJ
【 摘 要 】

Background and objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Methods: BEAS-2B cells treated with 3.0 μg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.

【 授权许可】

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