Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts

Hada, Megumi; Saganti, Premkumar B.; Cucinotta, Francis A.

doi:10.3390/ijms20184327

Title: Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts

Journal Article · Wed Sep 04 00:00:00 EDT 2019 · International Journal of Molecular Sciences (Online)

DOI:https://doi.org/10.3390/ijms20184327· OSTI ID:1560332

; Saganti, Premkumar B.; Cucinotta, Francis A.

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the contribution of NTE components in induced CA, we measured CA with and without an NO scavenger in normal skin fibroblasts cells after exposure to 600 MeV/u and 1 GeV/u 56Fe ions, less than one direct particle traversal per cell nucleus. Yields of CA were significantly lower in fibroblasts exposed to the NO scavenger compared to controls, suggesting involvement of NO in cell signaling for induction of CA. Media transferred from irradiated cells induced CA in non-irradiated cells, and this effect was abrogated with NO scavengers. Our results strongly support the importance of NTE contributions in the formation of CA at low-particle fluence in fibroblasts.

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Research Organization:: NASA Johnson Space Center, Houston, TX (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AI02-10ER64989; SC0002453

OSTI ID:: 1560332

Alternate ID(s):: OSTI ID: 1614623

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Vol. 20 Journal Issue: 18; ISSN 1422-0067

Publisher:: MDPI AGCopyright Statement

Country of Publication:: Switzerland

Language:: English

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Cited by: 2 works

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References (26)

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models Cucinotta, Francis A.; Cacao, Eliedonna Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-02087-3	journal	May 2017
The Bystander Effect Hall, Eric J. Health Physics, Vol. 85, Issue 1 https://doi.org/10.1097/00004032-200307000-00008	journal	January 2003
Overview of the NASA space radiation laboratory La Tessa, Chiara; Sivertz, Michael; Chiang, I-Hung Life Sciences in Space Research, Vol. 11 https://doi.org/10.1016/j.lssr.2016.10.002	journal	November 2016
Radiation-induced bystander effects — implications for cancer Seymour, Colin B.; Mothersill, Carmel Nature Reviews Cancer, Vol. 4, Issue 2 https://doi.org/10.1038/nrc1277	journal	February 2004
Epigenetics in radiation biology: a new research frontier Merrifield, Matt; Kovalchuk, Olga Frontiers in Genetics, Vol. 4 https://doi.org/10.3389/fgene.2013.00040	journal	January 2013
The role of DNA cluster damage and chromosome aberrations in radiation-induced cell killing: a theoretical approach Ballarini, F.; Altieri, S.; Bortolussi, S. Radiation Protection Dosimetry, Vol. 166, Issue 1-4 https://doi.org/10.1093/rpd/ncv135	journal	April 2015
Distribution of radiation-induced exchange aberrations in human chromosomes 1, 2 and 4 Luomahaara, S.; Lindholm, C.; Mustonen, R. International Journal of Radiation Biology, Vol. 75, Issue 12 https://doi.org/10.1080/095530099139151	journal	January 1999
Non-targeted effects and radiation-induced carcinogenesis: a review Burtt, Julie J.; Thompson, Patsy A.; Lafrenie, Robert M. Journal of Radiological Protection, Vol. 36, Issue 1 https://doi.org/10.1088/0952-4746/36/1/R23	journal	February 2016
Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects Matsuya, Yusuke; Sasaki, Kohei; Yoshii, Yuji Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-23202-y	journal	March 2018
Dose Response of γ Rays and Iron Nuclei for Induction of Chromosomal Aberrations in Normal and Repair-Deficient Cell Lines George, Kerry A.; Hada, Megumi; Jackson, Lori J. Radiation Research, Vol. 171, Issue 6 https://doi.org/10.1667/RR1680.1	journal	June 2009
Targeted and non-targeted effects of ionizing radiation Desouky, Omar; Ding, Nan; Zhou, Guangming Journal of Radiation Research and Applied Sciences, Vol. 8, Issue 2 https://doi.org/10.1016/j.jrras.2015.03.003	journal	April 2015
Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges Maeda, Junko; Yurkon, Charles R.; Fujii, Yoshihiro PLOS ONE, Vol. 10, Issue 12 https://doi.org/10.1371/journal.pone.0144619	journal	December 2015
The persistence of chromosome translocations in a radiation worker accidentally exposed to tritium Lucas, J. N.; Poggensee, M.; Straume, T. Cytogenetic and Genome Research, Vol. 60, Issue 3-4 https://doi.org/10.1159/000133353	journal	January 1992
AT cells are not radiosensitive for simple chromosomal exchanges at low dose Hada, Megumi; Huff, Janice L.; Patel, Zarana S. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 716, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2011.08.006	journal	November 2011
The Relative Biological Effect of High-Z, High-LET Charged Particles for Spermatogonial Killing Alpen, Edward L.; Powers-Risius, Patricia Radiation Research, Vol. 88, Issue 1 https://doi.org/10.2307/3575758	journal	October 1981
Cytogenetic damage in the blood lymphocytes of astronauts: Effects of repeat long-duration space missions George, K.; Rhone, J.; Beitman, A. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 756, Issue 1-2 https://doi.org/10.1016/j.mrgentox.2013.04.007	journal	August 2013
Chromosome aberrations induced by dual exposure of protons and iron ions Hada, M.; Meador, J. A.; Cucinotta, F. A. Radiation and Environmental Biophysics, Vol. 46, Issue 2 https://doi.org/10.1007/s00411-006-0083-y	journal	January 2007
Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings Cucinotta, Francis A.; Durante, Marco The Lancet Oncology, Vol. 7, Issue 5 https://doi.org/10.1016/S1470-2045(06)70695-7	journal	May 2006
Space Radiation Risks for Astronauts on Multiple International Space Station Missions Cucinotta, Francis A. PLoS ONE, Vol. 9, Issue 4 https://doi.org/10.1371/journal.pone.0096099	journal	April 2014
Non-targeted effects and the dose response for heavy ion tumor induction Cucinotta, Francis A.; Chappell, Lori J. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 687, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2010.01.012	journal	May 2010
Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B. PLOS ONE, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pone.0153998	journal	April 2016
Non-targeted and Delayed Effects of Exposure to Ionizing Radiation: I. Radiation-Induced Genomic Instability and Bystander Effects In Vitro Morgan, William F. Radiation Research, Vol. 159, Issue 5 https://doi.org/10.1667/0033-7587(2003)159[0567:NADEOE]2.0.CO;2	journal	May 2003
Werner Syndrome Protein Is Regulated and Phosphorylated by DNA-dependent Protein Kinase Yannone, Steven M.; Roy, Sashwati; Chan, Doug W. Journal of Biological Chemistry, Vol. 276, Issue 41 https://doi.org/10.1074/jbc.M101913200	journal	October 2001
Heavy ion carcinogenesis and human space exploration Durante, Marco; Cucinotta, Francis A. Nature Reviews Cancer, Vol. 8, Issue 6, p. 465-472 https://doi.org/10.1038/nrc2391	journal	May 2008
Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha -particle irradiated to nonirradiated cells Azzam, E. I. Proceedings of the National Academy of Sciences, Vol. 98, Issue 2 https://doi.org/10.1073/pnas.011417098	journal	January 2001
Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries Bonassi, S.; Norppa, H.; Ceppi, M. Carcinogenesis, Vol. 29, Issue 6 https://doi.org/10.1093/carcin/bgn075	journal	April 2008

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Biochemistry & Molecular Biology
Chemistry
ionizing radiation
chromosome aberrations
non-targeted effects

Title: Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts

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