title: Gene expression responses of HeLa cells to chemical species generated by an atmospheric plasma flow.
abstract: Plasma irradiation generates many factors able to affect the cellular condition, and this feature has been studied for its application in the field of medicine. We previously reported that hydrogen peroxide (H2O2) was the major cause of HeLa cell death among the chemical species generated by high level irradiation of a culture medium by atmospheric plasma. To assess the effect of plasma-induced factors on the response of live cells, HeLa cells were exposed to a medium irradiated by a non-lethal plasma flow level, and their gene expression was broadly analyzed by DNA microarray in comparison with that in a corresponding concentration of 51 μM H2O2. As a result, though the cell viability was sufficiently maintained at more than 90% in both cases, the plasma-medium had a greater impact on it than the H2O2-medium. Hierarchical clustering analysis revealed fundamentally different cellular responses between these two media. A larger population of genes was upregulated in the plasma-medium, whereas genes were downregulated in the H2O2-medium. However, a part of the genes that showed prominent differential expression was shared by them, including an immediate early gene ID2. In gene ontology analysis of upregulated genes, the plasma-medium showed more diverse ontologies than the H2O2-medium, whereas ontologies such as "response to stimulus" were common, and several genes corresponded to "response to reactive oxygen species." Genes of AP-1 proteins, e.g., JUN and FOS, were detected and notably elevated in the plasma-medium. These results showed that the medium irradiated with a non-lethal level of plasma flow altered various gene expressions of HeLa cells by giving not only common effects with H2O2 but also some distinctive actions. This study suggests that in addition to H2O2, other chemical species able to affect the cellular responses exist in the plasma-irradiated medium and provide unique features for it, probably increasing the oxidative stress level.
authors.affiliation: Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address: yokoyama@plasma.ifs.tohoku.ac.jp.
authors.forename: Mayo
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Histology and Embryology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Electronic address: kohei@shinshu-u.ac.jp.
authors.forename: Kohei
authors.initials: K
authors.lastname: Johkura
authors.affiliation: Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address: sato@ifs.tohoku.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sato
mesh_terms: D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017382:Reactive Oxygen Species
keywords: Gene expression; HeLa cell; Hydrogen peroxide; Microarray; Plasma flow; Reactive oxygen species