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

// Cheng-Lan Jiang 1, 2 , Shui-Wang He 1 , Yun-Dong Zhang 1, 3 , He-Xian Duan 1 , Tao Huang 4 , Yun-Chao Huang 5 , Gao-Feng Li 6 , Ping Wang 7 , Li-Ju Ma 8 , Guang-Biao Zhou 9 , Yi Cao 1 1 Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 2 Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming 650223, China 3 School of Life Sciences, University of Science and Technology of China, Hefei 230026, China 4 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 5 Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Kunming Medical University, (Yunnan Tumor Hospital), Kunming 650106, China 6 Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, (Yunnan Tumor Hospital), Kunming 650106, China 7 Department of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming 650032, China 8 Clinical Medicine Research Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650332, China 9 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Correspondence to: Yi Cao, email: caoy@mail.kiz.ac.cn , yicao1212@yahoo.de Guang-Biao Zhou, email: gbzhou@ioz.ac.cn Keywords: air pollution-related lung cancer, DNA methylation, benzo(a)pyrene, carcinogenesis, vitamin Received: August 20, 2016      Accepted: November 09, 2016      Published: November 25, 2016 ABSTRACT 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 pollution-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 down-regulation 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.