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. Overall design: Bisulphite converted DNA from the 102 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.

This dataset includes data for the manuscript in progress, Intracerebroventricular kynurenic acid modulation differentially regulates the immune and neuroendocrine stress response to acute ozone exposure. This study employed the use of kynurenic acid or the kynurenic acid synthesis inhibitor, PF-04859989 infused into the dorsal third ventricle of the brain in male WKY rats, prior to acute ozone exposure at 0.8 ppm, to evaluate the role of kynurenic acid in modulating the neuroendocrine stress response to ozone. Our results indicate that kynurenic acid may have a protective role in the brain, in attenuating the pulmonary and systemic effects of ozone exposure, perhaps through multiple mechanisms. This dataset is associated with the following publication: Rentschler, K., M.C. Schladweiler, R. Grindstaff, W. Williams, P.R. Kodavanti, D. Freeborn, L. Klein, G. Jung, D. Herr, P. Evansky, J. McKee, S. Gavett, and U. Kodavanti. Differential Effects of Intracerebroventricular Kynurenic Acid Regulation on the Inflammatory and Neuroendocrine Response to Acute Ozone Exposure. Presented at Society of Toxicology, Orlando, FL, USA, 03/16/2025 - 03/20/2025.

Methods: RNA-seq libraries were prepared using the Illumina TruSeq RNA kit and the TrueSeq method was employed for mRNA enrichment. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq1000 system. Reads were mapped on the Human Genome Reference and normalized expression table was generated. Results: Among differentially expressed genes 53 of them were up-regulated and 75 were down-regulated. Conclusions: Data demonstrate increased expression of genes associated with growth development and pro-survival in cardiac progenitors cultured under simulated microgravity compared with those cultured under standard gravity. RNA-sequencing analysis was performed to compare global gene expression profiles of cells at differentiation day 8 under simulated microgravity vs. standard gravity.

Background Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. Methods In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. Results Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. Conclusions These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth.

ATP binding cassette sub-family member 2 (ABCG2) is a well-defined efflux transporter found in various tissues. The role of ABCG2 during early embryonic development, however, is not established. Previous work suggested an association exists between xenobiotics that regulate Abcg2 transcription and differentiation of mouse embryonic stem cells (mESC), a relationship potentially related to redox homeostasis. ABCG2 was found to serve protective role in mESC as a xenobiotic transporter. The role of ABCG2 in regulating redox status, however, was unclear. The hypothesis that ABCG2 plays a fundamental role during mESC differentiation or that regulation of the receptor by xenobiotics may be associated with altered mESC differentiation could not be supported. This dataset is associated with the following publication: Rosen, M., S. Jeffay, H. Nichols, M. Hoopes, and S. Hunter. ATP Binding Cassette Sub-Family Member 2 (ABCG2) And Xenobiotic Exposure During Early Mouse Embryonic Stem Cell Differentiation. Birth Defects Research. John Wiley & Sons, Inc., Hoboken, NJ, USA, 110(1): 35-47, (2017).