Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Cells

Arsen Arakelyan¹  David. A. Goukassian²  Abrisham Eskandari²  Mary K. Khlgatian²  Malik Bisserier²  Agnieszka Brojakowska²  Kenneth M. Fish²  Lahouaria Hadri²  Maria Cimini³  Anamika Bajpai³  May M. Truongcao³  Vandana Malaredy³  Raj Kishore³  Venkata Naga Srikanth Garikipati⁴  Sankar Addya⁵  Eleanor A. Blakely⁶  Polly Y. Chang⁷ 

[1] Bioinformatics Group, The Institute of Molecular Biology, The National Academy of Sciences of the Republic of Armenia, Yerevan 0014, Armenia;Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA;Department of Emergency Medicine, Dorothy M Davis Heart and Lung Research Institute, Wexner Medical School, The Ohio State University, Columbus, OH 43210, USA;Kimmel Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA;Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;SRI International, Menlo Park, CA 94025, USA;

关键词: heart;    space radiation;    gene expression;    gamma radiation;    NASA;    female mice;   

DOI  :  10.3390/cells10020387

来源: DOAJ

【 摘 要 】

Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR ¹³⁷Cs (40-160 cGy, 0.662 MeV), ¹⁴Si-IR (4-32 cGy, 260 MeV/n), or ²²Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in ¹⁴Si- and ²²Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.

【 授权许可】

Unknown