Long-term effects of very low dose particle radiation on gene expression in the heart: Degenerative disease risks

Venkata Naga Srikanth Garikipati, Arsen Arakelyan, Eleanor A. Blakely, Polly Y. Chang, May M. Truongcao, Maria Cimini, Vandana Malaredy, Anamika Bajpai, Sankar Addya, Malik Bisserier, Agnieszka Brojakowska, Abrisham Eskandari, Mary K. Khlgatian, Lahouaria Hadri, Kenneth M. Fish, Raj Kishore, David A. Goukassian

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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-IR137Cs (40-160 cGy, 0.662 MeV),14Si-IR (4-32 cGy, 260 MeV/n), or22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months postexposure, 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 14 Si-and22Ti-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.

Original languageEnglish
Article number387
Pages (from-to)1-25
Number of pages25
JournalCells
Volume10
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • Female mice
  • Gamma radiation
  • Gene expression
  • Heart
  • NASA
  • Space radiation

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