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Gene expression profiles in human malignant melanoma cell lines exposed to carbon ions or X-rays

ABSTRACT: Little is known about molecular mechanism for its effectiveness of C-ions in melanomas. In this study, we examined the cytotoxic effects of C-ions on 6 human malignant melanoma cell lines, and gene expression profiles and cell cycle progression were also examined to reveal the mechanism of the therapeutic effectiveness of C-ions. Equivalent doses of the C-ions were more effective at reducing the survival rates than X-rays, and the relative biological effectiveness (RBE) was > 2.0 in all cell lines. In unsupervised 2D clustering performed for C-ions irradiated groups at 1 h after irradiation, many of the probes were down-regulated among 6 cell lines. We identified probes, such as XKRY, ELA3A, T-STAR, SCN9A, ELA2A, CRK7, CCNA2, CROP, CYR61, SDFR1, and SMAD4 differentially responded to C-ions and X-rays among 4 cell lines. CCNA2 was down-regulated by C-ions more than X-rays at 3 h after irradiation, and C-ions induced G2/M arrest more than X-rays in three cell lines at 30 h. Many of p53 target genes, such as ATF3, BTG2, CDKN1A, GADD45A, SESN1, and TNFRSF6 were up-regulated by C-ions at 3 h. The expressions of p53 target genes were not changed in HMV-I and MeWo. In MeWo, APG3L, RPL26 and PCNA were down-regulated or E2F2 and LIMS3 were up-regulated, and in HMV-I, ATF3, FOS, and CYR61 were up-regulated at 1 h after C-ions. In conclusion, C-ions affected p53-dependent and p53-independent pathways of cell death and cell cycle. Individual mechanism in activating of cell death was observed in each cell line of 6 melanomas. Keywords: Specific gene expression prfiles after carbon ion irradiation

ORGANISM(S): Homo sapiens

PROVIDER: GSE6630 | GEO | 2008/06/01

SECONDARY ACCESSION(S): PRJNA98859

REPOSITORIES: GEO

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Project description:Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 28Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and edges (“shores”) of CpG islands. The 28Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56Fe ion irradiation sensitive sites, but not those affected by X ray or 28Si ions, could discriminate tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. The 56Fe ion signature may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space. Genome wide DNA methylation profiling of normal human bronchial epithelial cells irradiated with varying doses of 28Si-ion radiation ( 300 MeV/u at 0, 0.3, 1.0 Gy) , 56Fe-ion radiation (600 MeV/u at 0, 0.1, 0.3, 1.0 Gy) or X rays (320 kV at 0, 1.0 Gy). Triplicate control and irradiated samples were incubated and sampled at 4 timepoints between 2 and 62 days. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across >485,000 CpGs from collected samples. Samples include: 56Fe ions, 4 doses x 4 time points x 3 replicates (4 removed in QC) = 44 samples; 28Si ions = 3 doses x 4 time points x 3 replicates = 36 samples; X ray, 2 doses x 4 time points x 3 replicates (2 removed in QC)= 22 samples.

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Gene expression profiles in human malignant melanoma cell lines exposed to carbon ions or X-rays

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