title: Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study.
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.
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.|Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Cheng-Lan
authors.initials: CL
authors.lastname: Jiang
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Shui-Wang
authors.initials: SW
authors.lastname: He
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: He-Xian
authors.initials: HX
authors.lastname: Duan
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Kunming Medical University, (Yunnan Tumor Hospital), Kunming 650106, China.
authors.forename: Yun-Chao
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, (Yunnan Tumor Hospital), Kunming 650106, China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Clinical Medicine Research Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650332, China.
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity; D045744:Cell Line, Tumor; D019175:DNA Methylation; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D025101:Vitamin B 6 / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D012333:RNA, Messenger; D001564:Benzo(a)pyrene; D025101:Vitamin B 6; D001205:Ascorbic Acid
keywords: DNA methylation; air pollution-related lung cancer; benzo(a)pyrene; carcinogenesis; vitamin