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Only two genes were found to be HIF dependent. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Nine genes were altered in response to chronic hypoxia in all 17 studies. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation.

Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Results : We examined the effect of chronic hypoxia (3 days 0.5% oxygen) on human brain micro endothelial cells (HBMEC) viability and apoptosis. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Mata-Greenwood, Eugenia Goyal, Dipali Goyal, Raviīackground : Hypoxia inducible factor 1 alpha (HIF1A) is a master regulator of acute hypoxia however, with chronic hypoxia, HIF1A levels return to the normoxic levels. 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.Ĭomparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells 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. 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. 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. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. 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. 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. Jiang, Cheng-Lan He, Shui-Wang Zhang, Yun-Dong Duan, He-Xian Huang, Tao Huang, Yun-Chao Li, Gao-Feng Wang, Ping Ma, Li-Ju Zhou, Guang-Biao Cao, Yi Despite the fact that in some cases, some pathologists may make mistakes in the histopathological diagnosis of oral lichen planus, the results obtained in this study show that the alterations present in oral lichen planus differ considerably from those seen in epidermoid carcinoma, thus showing how distinct these two diseases are.Īir pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. As to the types of alterations, the chi-squared test also revealed statistically significant differences among the lesions assessed in relation to the following cell alterations: nuclear excess chromatism, atypical mitoses, cellular pleomorphism and abnormal cell differentiation (p<0.05). The Student t test (alpha=5%) revealed a statistically significant difference between the average number of cell alterations in oral lichen planus (5.87+/-1.57) and in epidermoid carcinoma (7.60+/-1.81). The most frequently found alterations in oral lichen planus were: an increase in the nucleus/cytoplasm relation (93.33%), nucleus membrane thickness (86.67%) and bi-nucleus or multinucleous (86.67%). Histological cross-sections of oral lichen planus and epidermoid carcinoma, dyed by hematoxylineosin, were analyzed through light microscopy. The present study aims at analyzing the alterations found in the epithelial cells present in the oral cavity lichen planus, comparing them to those found in epidermoid carcinoma. Sousa, Fernando Augusto Cervantes Garcia de Paradella, Thaís Cachuté Brandão, Adriana Aigotti Haberbeck Rosa, Luiz Eduardo BlumerĬurrently, much is discussed regarding the pre-malignant nature of mouth mucosa lichen planus. Comparative study of cell alterations in oral lichen planus and epidermoid carcinoma of the mouth mucosa.