skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"

Abstract

Low dose ionizing radiation effects are difficult to study in human population because of the numerous confounding factors such as genetic and lifestyle differences. Research in mammalian model systems and in vitro is generally used in order to overcome this difficulty. In this program project three projects have joined together to investigate effects of low doses of ionizing radiation. These are doses at and below 10 cGy of low linear energy transfer ionizing radiation such as X-ray and gamma rays. This project was focused on cellular signaling associated with nuclear factor kappa B (NFkB) and mitochondria - subcellular organelles critical for cell aging and aging-like changes induced by ionizing radiation. In addition to cells in culture this project utilized animal tissues accumulated in a radiation biology tissue archive housed at Northwestern University (http://janus.northwestern.edu/janus2/index.php). Major trust of Project 1 was to gather all of the DoE sponsored irradiated animal (mouse, rat and dog) data and tissues under one roof and investigate mitochondrial DNA changes and micro RNA changes in these samples. Through comparison of different samples we were trying to delineate mitochondrial DNA quantity alterations and micro RNA expression differences associated with different doses and dose rates of radiation. Historic animalmore » irradiation experiments sponsored by DoE were done in several national laboratories and universities between 1950’s and 1990’s; while these experiments were closed data and tissues were released to Project 1. Project 2 used cells in culture to investigate effects that low doses or radiation have on NFκB and its target genes manganese superoxide dismutase (MnSOD) and genes involved in cell cycle: Cyclins (B1 and D1) and cyclin dependent kinases (CDKs). Project 3 used cells in culture such as “normal” human cells (breast epithelial cell line MCF10A cells and skin keratinocyte cells HK18) and mouse embryo fibroblast (mef) cells to focus on role of NFkB protein and several other proteins such as survivin (BIRC5) in radiation dependent regulation of tumor necrosis factor alpha (TNFα) and its downstream signaling.« less

Authors:
ORCiD logo [1];  [2];  [3]
  1. Northwestern Univ., Evanston, IL (United States)
  2. Univ. of Chicago, IL (United States)
  3. Univ. of California, Davis, CA (United States)
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1362082
Report Number(s):
DOE-NU-SC0001271
DOE Contract Number:
SC0001271
Resource Type:
Technical Report
Resource Relation:
Related Information: http://janus.northwestern.edu/janus2/index.php
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; low dose ionizing radiation; animal models; data and tissue archives; nuclear factor kappa B

Citation Formats

Woloschak, Gayle E, Grdina, David, and Li, Jian-Jian. Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria". United States: N. p., 2017. Web. doi:10.2172/1362082.
Woloschak, Gayle E, Grdina, David, & Li, Jian-Jian. Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria". United States. doi:10.2172/1362082.
Woloschak, Gayle E, Grdina, David, and Li, Jian-Jian. Mon . "Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"". United States. doi:10.2172/1362082. https://www.osti.gov/servlets/purl/1362082.
@article{osti_1362082,
title = {Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"},
author = {Woloschak, Gayle E and Grdina, David and Li, Jian-Jian},
abstractNote = {Low dose ionizing radiation effects are difficult to study in human population because of the numerous confounding factors such as genetic and lifestyle differences. Research in mammalian model systems and in vitro is generally used in order to overcome this difficulty. In this program project three projects have joined together to investigate effects of low doses of ionizing radiation. These are doses at and below 10 cGy of low linear energy transfer ionizing radiation such as X-ray and gamma rays. This project was focused on cellular signaling associated with nuclear factor kappa B (NFkB) and mitochondria - subcellular organelles critical for cell aging and aging-like changes induced by ionizing radiation. In addition to cells in culture this project utilized animal tissues accumulated in a radiation biology tissue archive housed at Northwestern University (http://janus.northwestern.edu/janus2/index.php). Major trust of Project 1 was to gather all of the DoE sponsored irradiated animal (mouse, rat and dog) data and tissues under one roof and investigate mitochondrial DNA changes and micro RNA changes in these samples. Through comparison of different samples we were trying to delineate mitochondrial DNA quantity alterations and micro RNA expression differences associated with different doses and dose rates of radiation. Historic animal irradiation experiments sponsored by DoE were done in several national laboratories and universities between 1950’s and 1990’s; while these experiments were closed data and tissues were released to Project 1. Project 2 used cells in culture to investigate effects that low doses or radiation have on NFκB and its target genes manganese superoxide dismutase (MnSOD) and genes involved in cell cycle: Cyclins (B1 and D1) and cyclin dependent kinases (CDKs). Project 3 used cells in culture such as “normal” human cells (breast epithelial cell line MCF10A cells and skin keratinocyte cells HK18) and mouse embryo fibroblast (mef) cells to focus on role of NFkB protein and several other proteins such as survivin (BIRC5) in radiation dependent regulation of tumor necrosis factor alpha (TNFα) and its downstream signaling.},
doi = {10.2172/1362082},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Mon Jun 12 00:00:00 EDT 2017},
month = {Mon Jun 12 00:00:00 EDT 2017}
}

Technical Report:

Save / Share:
  • This grant was designed to examine the cellular and molecular mechanisms for the bystander effect of radiation (initially described in this laboratory) whereby damage signals are passed from irradiated to non-irradiated cells in a population. These signals induce genetic effects including DNA damage, mutations and chromosomal aberrations in the nonirradiated cells. Experiments were carried out in cultured mammalian cells, primarily human diploid cells, irradiated with alpha particles. This research resulted in 17 publications in the refereed literature and is described in the Progress Report where it is keyed to the publication list. This project was initiated at the Harvard Schoolmore » of Public Health (HSPH) and continued in collaboration with students/fellows at Colorado State University (CSU) and the New Jersey Medical School (NJMS).« less
  • The DNA of each individual is subject to formation of some 2-4 x 10/sup 14/ ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If themore » probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis.« less
  • Data on the relationship between the radiation dose and its somatic effects, those apparent in the irradiated generation, in mammals were collected in order to determine whether any dose of radiation was followed by those effects or if a threshold dose existed below which no effect occurred. The effects studied were acute death, body weight loss and organ atrophy, depression of mitotic activity, induction of lens opacity, depression of fron uptake by erythrodytes and erythrocyte-forming tissue, suporession of defense mechanisms, induction of turaor development, radiation-induced leukemia in man, and shortening of the life-span. No experiments performed were able to givemore » conclusive evidence of the existence or non-existence of the threshold. (M.C.G.)« less
  • The mechanical property results for two high quality beryllium materials subjected to low temperature, low dose neutron irradiation in water moderated reactors are presented. Materials chosen were the S65-C ITER candidate material produced by Brush Wellman, and Kawecki Berylco Industries P0 beryllium. Both materials were processed by vacuum hot pressing. Mini sheet tensile and thermal diffusivity specimens were irradiated in the temperature range of {approximately}100--275 C from a fast (E > 0.1 MeV) neutron dose of 0.05 to 1.0 {times} 10{sup 25} n/m{sup 2} in the High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory and the Highmore » Flux Beam Reactor (HFBR) at the Brookhaven National Laboratory. As expected from earlier work on beryllium, both materials underwent significant embrittlement with corresponding reduction in ductility and increased strength. Both thermal diffusivity and volumetric expansion were measured and found to be negligible in this temperature and fluence range. Of significance from this work is that while both materials rapidly embrittle at these ITER relevant irradiation conditions, some ductility (>1--2%) remains, which contrasts with a body of earlier work including recent work on the Brush-Wellman S65-C material irradiated to slightly higher neutron fluence.« less
  • Twenty-four monkeys (Macaca mulatta) were divided into four groups of six and exposed periodically to low doses of neutrons from Po-Be sources. The irradiated groups received 13, 28, and 55 rep total dose, which was divided into doses administered every 4 days for 40 exposures. The cellular elements of the peripheral blood, hemoglobin, and hematocrit values were sampled and enumerated at intervals postirradiation. These data were analyzed by analysis of variance. All surviving monkeys reestablished normal hematologic values by the end of 24 weeks postirradiation. There was no indication of any incapacitating injury under these experimental conditions. A significant statisticalmore » result was found for reticulocytes, hematocrit values, neutrophils, and lymphocytes. Only the hematocrit value changes are considered interpretable in terms of the irradiation treatment. (auth) 385O A cutaneous fibrosarcoma with metastases was observed four years after localized beta irradiation of the skin. Ths gross and microscopic appearance of the primary lesion and its metastases are described. (auth)« less