Abstract：
:Proton exposure induces mutations and cancer, which are presumably linked. Because protons are abundant in the space environment and significant uncertainties exist for the effects of space travel on human health, the purpose of this study was to identify the types of mutations induced by exposure of mammalian cells to 4-5 Gy of 1 GeV protons. We used an assay that selects for mutations affecting the chromosome 8-encoded Aprt locus in mouse kidney cells and selected mutants after proton exposure both in vivo and in cell culture. A loss of heterozygosity (LOH) assay for DNA preparations from the in vivo-derived kidney mutants revealed that protons readily induced large mutational events. Fluorescent in situ hybridization painting for chromosome 8 showed that >70% of proton-induced LOH patterns resembling mitotic recombination were in fact the result of nonreciprocal chromosome translocations, thereby demonstrating an important role for DNA double-strand breaks in proton mutagenesis. Large interstitial deletions, which also require the formation and resolution of double-strand breaks, were significantly induced in the cell culture environment (14% of all mutants), but to a lesser extend in vivo (2% of all mutants) suggesting that the resolution of proton-induced double-strand breaks can differ between the intact tissue and cell culture microenvironments. In total, the results demonstrate that double-strand break formation is a primary determinant for proton mutagenesis in epithelial cell types and suggest that resultant LOH for significant genomic regions play a critical role in proton-induced cancers.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Turker MS,Grygoryev D,Dan C,Eckelmann B,Lasarev M,Gauny S,Kwoh E,Kronenberg Adoi
10.1667/RR3174.1subject
Has Abstractpub_date
2013-05-01 00:00:00pages
521-9issue
5eissn
0033-7587issn
1938-5404journal_volume
179pub_type
杂志文章abstract：:The well-established process of potentially lethal damage (PLD) repair enhances plateau-phase cell survival after exposure to ionizing radiation. PLD repair requires that confluent cells be incubated prior to plating for a colony-forming assay rather than being plated immediately. Enhanced double-strand break (DSB) re...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr1423.1
更新日期：2008-10-01 00:00:00
abstract：:Several lines of correlative evidence link transforming growth factor alpha (Tgfa, also known as TGF-alpha) to proliferative activity in jejunal crypt cells. It is therefore tempting to hypothesize that, as a ligand of the epidermal growth factor, it mediates the compensatory proliferative burst in the crypts after ra...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)155[0866:tpromj]2.0.co;2
更新日期：2001-06-01 00:00:00
abstract：:In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there e...
journal_title：Radiation research
pub_type：
doi：10.1667/RR14810.1
更新日期：2017-08-01 00:00:00
abstract：:Studies were conducted to determine the effects of BeSO4 or X rays, alone and in combination, on cell cycle kinetics, cell killing, and the production of chromosome aberrations in Chinese hamster ovary (CHO) cells. The concentration of BeSO4 required to kill 50% of CHO cells exposed to BeSO4 for 20 h was determined to...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
abstract：:There is an ongoing and significant need for radiation countermeasures to reduce morbidities and mortalities associated with exposure of the heart and lungs from a radiological or nuclear incidents. Radiation-induced late effects occur months to years after exposure, stemming from significant tissue damage and remodel...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR14403.2
更新日期：2016-11-01 00:00:00
abstract：:There is strong evidence that biological response to ionizing radiation has a contribution from unirradiated "bystander" cells that respond to signals emitted by irradiated cells. We discuss here an approach incorporating a radiobiological bystander response, superimposed on a direct response due to direct energy depo...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)155[0402:tbeiro]2.0.co;2
更新日期：2001-03-01 00:00:00
abstract：:In a patient with Morbus Hodgkin, structural aberrations of the chromosome type in peripheral lymphocytes were analyzed during radiation therapy (accumulated target dose 44.6 Gy: 22 fractions of 1.8 Gy each and 2 fractions of 2.5 Gy each at the end of the therapy). The blood was sampled about 5 min after a fraction an...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Pentamidine is similar to rhodamine-123 in chemical structure and state of electron charge, and rhodamine-123 was previously shown to be a hyperthermic sensitizer under appropriate cell culture conditions. The present experiments were carried out to determine whether pentamidine would potentiate hyperthermic cell kill...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Ionizing radiation induces clustered DNA damage sites, whereby two or more individual DNA lesions are formed within one or two helical turns of DNA by a single radiation track. A subset of DNA clustered damage sites exist in which the lesions are located in tandem on the same DNA strand. Recent studies have establishe...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3284
更新日期：2005-01-01 00:00:00
abstract：:Hormetic and adaptive responses induced by low-level radiation in hematopoietic and immune systems have been observed, as shown by stimulatory effects on cell growth and resistance to subsequent radiation-induced cytogenetic damage. However, in terms of cell death by apoptosis, the effects of low-level radiation are c...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3528.1
更新日期：2006-04-01 00:00:00
abstract：:Breast tissue is very susceptible to radiation-induced carcinogenesis, and mammary stem/progenitor cells are potentially important targets of this. The mammary epithelium is maintained as two mostly independent lineages of luminal and basal cells. To elucidate their immediate radiation responses, we analyzed the mamma...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR15566.1
更新日期：2020-07-08 00:00:00
abstract：:Prior to whole-liver irradiation (0, 15, 25 Gy) rats were not treated, placed on a protein-deficient diet for 2 weeks, administered cyclophosphamide, and/or depleted of intracellular glutathione by injection with buthionine sulfoximide and diethyl maleate. At various times (0 to 84 days) after 0- and 25-Gy liver irrad...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:Abstract The present study was undertaken to investigate the ability of dietary supplements to reduce the formation and severity of cataracts in mice irradiated with high-energy protons or iron ions, which are important components of the radiation encountered by astronauts during space travel. The mice were exposed to...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1398.1
更新日期：2010-03-01 00:00:00
abstract：:Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. High-throughput radiati...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RADE-20-00042.1
更新日期：2020-10-16 00:00:00
abstract：:The radiation dose received by crew members in interplanetary space is influenced by the stage of the solar cycle. Using the recently developed models of the galactic cosmic radiation (GCR) environment and the energy-dependent radiation transport code, we have calculated the dose at 0 and 5 cm water depth; using a com...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Radiation exposure from a number of terrestrial sources is associated with an increased risk for atherosclerosis. Recently, concern over whether exposure to cosmic radiation might pose a similar risk for astronauts has increased. To address this question, we examined the effect of 2 to 5 Gy iron ions ((56)Fe), a parti...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2482.1
更新日期：2011-06-01 00:00:00
abstract：:Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear en...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
abstract：:The modifying effects of m-aminobenzamide (m-ABA), an inhibitor of poly(ADP-ribose) synthesis, on 42 degrees C hyperthermia- and/or radiation-induced cell killing were examined in Chinese hamster V-79 cells. When cells were exposed to 42 degrees C hyperthermia in combination with m-ABA (10 mM), cell survival decreased...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:We studied the role of cysteine as an intracellular radiation protector under conditions in which both oxygen and thiols were monitored at 37 degrees C. In HCT-116 human colon cancer cells, the intracellular cysteine content affects the radiation survival dramatically at intermediate oxygen levels, but not at zero or ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)156[0388:tkmfro]2.0.co;2
更新日期：2001-10-01 00:00:00
abstract：:The high-energy neutron component of the space radiation environment in thick structures such as the International Space Station contributes to the total radiation dose received by an astronaut. Detector design constraints such as size and mass have limited the energy range of neutron spectrum measurements in orbit to...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2003)159[0154:henswt]2.0.co;2
更新日期：2003-02-01 00:00:00
abstract：:In previous studies we determined a gene expression signature in baboons for predicting the severity of hematological acute radiation syndrome. We subsequently validated a set of eight of these genes in leukemia patients undergoing total-body irradiation. In the current study, we addressed the effect of intra-individu...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR15013.1
更新日期：2018-09-01 00:00:00
abstract：:In the analysis of the effects of radiation or drugs on clonogenic survival data of mammalian cells, it is often advantageous to compare entire dose-response curves generated under different experimental conditions rather than to conduct single-dose comparisons. We propose a two-stage method for the global comparison ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Wortmannin has been shown to be an efficient radiosensitizer. Since wortmannin is able to inhibit DNA-dependent protein kinase (DNA-PK) and double-strand break (DSB) rejoining, it is believed that its mechanism of radiation sensitization is through the inhibition of DNA-PK-mediated repair of DSBs. However, since wortm...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:This study investigated whether tetrachlorodecaoxide (TCDO), a potent wound-healing agent, promotes recovery of hematopoietic tissue of mice depleted by sublethal X irradiation. Mice were exposed to 3 Gy total-body irradiation and were given 1 ml/kg TCDO intravenously daily from day 1 to 5 or day 4 to 8 after irradiat...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:Our data (Reddy et al., Radiat. Res. 141, 252-258, 1995) on the kinetics of the repair of potentially lethal damage in log-phase Chinese hamster V79 cells are used to test some predictions which arise from the different assumptions of the repair-misrepair (RMR) (C. A. Tobias, Radiat. Res. 104, S77-S95, 1985), lethal-p...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:The lineal energy distribution and several other dosimetric parameters were measured for the neutrons emitted from a replica of the Hiroshima bomb to determine their usefulness in biological experiments designed to estimate the effectiveness of actual Hiroshima neutrons. The "Little-Boy" replica (LBR) was constructed ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Mitochondrial DNA heteroplasmy using the protein-coding cytochrome b (Mtcyb) gene was assessed in laboratory mice (C57BL/6 and BALB/c) exposed to the Chernobyl environment. Subacute to subchronic (30-40 days) exposure resulted in a cumulative radiation dose of 1.2-1.6 Gy ( approximately 0.04 Gy/day). Mice were sampled...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2003)159[0458:mdhilm]2.0.co;2
更新日期：2003-04-01 00:00:00
abstract：:Bcl-X(S) is a pro-apoptosis member of the Bcl2 family that has been shown to induce cell death and enhance chemosensitivity. We have investigated the effect of Bcl-X(S) overexpression on radiation sensitivity. Using a tetracycline-repressible system, we found that removal of tetracycline for 16 h induced Bcl-X(S) and ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3169
更新日期：2004-05-01 00:00:00
abstract：:Electron microbeam experiments are planned or under way to explore in part the question regarding whether the bystander effect is a general phenomenon or is restricted to high-LET radiation. Since low-LET radiations scatter more readily compared to high-LET radiations, identifying bystander cells and assessing the pot...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)155[0089:moakem]2.0.co;2
更新日期：2001-01-01 00:00:00
abstract：:The International Commission on Radiation Protection (ICRP) has lowered the dose limits for workers and for the general public exposed to ionizing radiation. Consequently, a reliable dosimetric method for monitoring possible radiation-induced damage is of great importance in radioprotection. The counting of dicentric ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR3544.1
更新日期：2006-05-01 00:00:00
