TY - JOUR
T1 - Long-term effects of very low dose particle radiation on gene expression in the heart
T2 - Degenerative disease risks
AU - Garikipati, Venkata Naga Srikanth
AU - Arakelyan, Arsen
AU - Blakely, Eleanor A.
AU - Chang, Polly Y.
AU - Truongcao, May M.
AU - Cimini, Maria
AU - Malaredy, Vandana
AU - Bajpai, Anamika
AU - Addya, Sankar
AU - Bisserier, Malik
AU - Brojakowska, Agnieszka
AU - Eskandari, Abrisham
AU - Khlgatian, Mary K.
AU - Hadri, Lahouaria
AU - Fish, Kenneth M.
AU - Kishore, Raj
AU - Goukassian, David A.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Female mice
KW - Gamma radiation
KW - Gene expression
KW - Heart
KW - NASA
KW - Space radiation
UR - http://www.scopus.com/inward/record.url?scp=85102687319&partnerID=8YFLogxK
U2 - 10.3390/cells10020387
DO - 10.3390/cells10020387
M3 - Article
C2 - 33668521
AN - SCOPUS:85102687319
SN - 2073-4409
VL - 10
SP - 1
EP - 25
JO - Cells
JF - Cells
IS - 2
M1 - 387
ER -