Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study

Cheng-Lan Jiang, Shui-Wang He, Yun-Dong Zhang, He-Xian Duan, Tao Huang, Yun-Chao Huang, Gao-Feng Li, Ping Wang, Li-Ju Ma, Guang-Biao Zhou, Yi Cao
2016 OncoTarget  
The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air
more » ... ion-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to downregulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.
doi:10.18632/oncotarget.13622 pmid:27901495 pmcid:PMC5352062 fatcat:npbar6bzd5hzvmepeebzs47nsu