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

Abstract

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 atmore » low-particle fluence in fibroblasts.« less

Authors:
ORCiD logo; ;
Publication Date:
Research Org.:
NASA Johnson Space Center, Houston, TX (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1560332
Alternate Identifier(s):
OSTI ID: 1614623
Grant/Contract Number:  
AI02-10ER64989; SC0002453
Resource Type:
Published Article
Journal Name:
International Journal of Molecular Sciences (Online)
Additional Journal Information:
Journal Name: International Journal of Molecular Sciences (Online) Journal Volume: 20 Journal Issue: 18; Journal ID: ISSN 1422-0067
Publisher:
MDPI AG
Country of Publication:
Switzerland
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biochemistry & Molecular Biology; Chemistry; ionizing radiation; chromosome aberrations; non-targeted effects

Citation Formats

Hada, Megumi, Saganti, Premkumar B., and Cucinotta, Francis A. Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts. Switzerland: N. p., 2019. Web. https://doi.org/10.3390/ijms20184327.
Hada, Megumi, Saganti, Premkumar B., & Cucinotta, Francis A. Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts. Switzerland. https://doi.org/10.3390/ijms20184327
Hada, Megumi, Saganti, Premkumar B., and Cucinotta, Francis A. Wed . "Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts". Switzerland. https://doi.org/10.3390/ijms20184327.
@article{osti_1560332,
title = {Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts},
author = {Hada, Megumi and Saganti, Premkumar B. and Cucinotta, Francis A.},
abstractNote = {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.},
doi = {10.3390/ijms20184327},
journal = {International Journal of Molecular Sciences (Online)},
number = 18,
volume = 20,
place = {Switzerland},
year = {2019},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3390/ijms20184327

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