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Metabolites
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Metabolomics/Lipidomics in Radiation Research
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Metabolomics/Lipidomics in Radiation Research

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (30 August 2020) | Viewed by 19469

Special Issue Editor

Dr. Evagelia C. Laiakis

E-Mail Website
Guest Editor
Department of Oncology, Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, USA
Interests: biodosimetry; space radiation; low dose and low dose rate; radiotherapy; radioprotectors/mitigators

Special Issue Information

Dear Colleagues,

We are pleased to announce a Special Issue of the journal Metabolites dedicated to metabolomic and lipidomic responses to ionizing radiation. Metabolomics and lipidomics have contributed significant knowledge to basic and more clinically oriented research and, together with other -omics technologies, can provide a holistic view in a cellular, tissue, or systemic level. This issue will aim to incorporate novel and review papers from a wide range of key topics in the radiation research field. Normal tissue responses, tumor and tumor microenvironment, radiation quality, dose and dose rate effects, metabolic responses to radioprotectors and mitigators, and biomarkers in tissues (including tissue imaging) and biofluids are key topics in the radiation research field. Papers will be published as accepted and assembled in the Special Issue appearing in 2020.

Dr. Evagelia C. Laiakis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biodosimetry and biomarkers
  • Low dose and dose rate effects
  • Space radiation
  • Radioprotectors/mitigators
  • Normal tissue and tumor responses

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Published Papers (6 papers)

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Research

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11 pages, 1623 KiB  
Article
Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates
by Heng-Hong Li, Yun-Tien Lin, Evagelia C. Laiakis, Maryam Goudarzi, Waylon Weber and Albert J. Fornace, Jr.
Metabolites 2020, 10(7), 270; https://doi.org/10.3390/metabo10070270 - 30 Jun 2020
Cited by 7 | Viewed by 2503
Abstract
Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples [...] Read more.
Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples from mice exposed to 137Cs internal emitters. Animals were injected intraperitoneally with 137CsCl solutions of varying radioactivity, and the absorbed doses were calculated. To determine the dose rate effect, serum samples were collected at 2, 3, 5, 7, and 14 days after injection. Based on the time for each group receiving the cumulative dose of 4 Gy, the dose rate for each group was determined. The dose rates analyzed were 0.16 Gy/day (low), 0.69 Gy/day (medium), and 1.25 Gy/day (high). The results indicated that at a cumulative dose of 4 Gy, the low dose rate group had the least number of statistically significantly differential spectral features. Some identified metabolites showed common changes for different dose rates. For example, significantly altered levels of oleamide and sphingosine 1-phosphate were seen in all three groups. On the other hand, the intensity of three amino acids, Isoleucine, Phenylalanine and Arginine, significantly decreased only in the medium dose rate group. These findings have the potential to be used in assessing the exposure and the biological effects of internal emitters. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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14 pages, 2252 KiB  
Article
Effects of Genetic Variation on Urinary Small Molecule Signatures of Mice after Exposure to Ionizing Radiation: A Study of p53 Deficiency
by Evan L. Pannkuk, Evagelia C. Laiakis, Pelagie Ake, Steven J. Strawn, Yi-Wen Wang and Albert J. Fornace
Metabolites 2020, 10(6), 234; https://doi.org/10.3390/metabo10060234 - 8 Jun 2020
Cited by 6 | Viewed by 2530
Abstract
Due to risks from potential exposures to ionizing radiation (IR), improved radiological countermeasures are required, as well as rapid high-throughput biodosimetry. Genotypic variation in the general population contributes to differences in radiosensitivity that may affect biodosimetry accuracy. Previous studies utilized radiosensitive mutant mouse [...] Read more.
Due to risks from potential exposures to ionizing radiation (IR), improved radiological countermeasures are required, as well as rapid high-throughput biodosimetry. Genotypic variation in the general population contributes to differences in radiosensitivity that may affect biodosimetry accuracy. Previous studies utilized radiosensitive mutant mouse models (Parp1−/− and Atm−/−) to determine the effects of genotypic deficiency on radiation signatures. Here, we extend this approach by examining changes in the urinary metabolome in a hematopoietic (HP) resistant mouse model (p53−/−) after IR exposure. As p53 is a primary regulator in radiation response and apoptosis, limited hematopoietic stem cell apoptosis leads to reduced mortality at doses of ~8–10 Gy but increased mortality at higher doses (>15 Gy) due to mitotic catastrophe in gastrointestinal (GI) crypt cells. Urine was collected from mice (wild-type (WT), p53+/−, and p53−/−) pre-irradiation and at 4 and 24 h after total body irradiation (TBI) (WT: 8 and 10 Gy; p53−/−: 10 Gy) for metabolic phenotyping using an ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platform. Minimal differences were detected between unirradiated WT, p53+/−, and p53−/− mice. While similar perturbations were observed for metabolites involved in tryptophan, vitamin B6, and histamine pathways, glycine conjugation, and redox metabolism for WT and p53−/− mice after TBI, an overall dampened response was observed in p53-deficient mice. Despite comparable metabolite patterns between genotypes, differentiation was achieved through receiver operating characteristic curve analysis with high specificity and sensitivity for carnitine, N1-acetylspermidine, and creatine. These studies highlight that both attenuated and dampened metabolic responses due to genetic variability in the general population need to be addressed in biodosimetry frameworks. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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14 pages, 4439 KiB  
Article
Alterations in Tissue Metabolite Profiles with Amifostine-Prophylaxed Mice Exposed to Gamma Radiation
by Amrita K. Cheema, Yaoxiang Li, Michael Girgis, Meth Jayatilake, Oluseyi O. Fatanmi, Stephen Y. Wise, Thomas M. Seed and Vijay K. Singh
Metabolites 2020, 10(5), 211; https://doi.org/10.3390/metabo10050211 - 21 May 2020
Cited by 21 | Viewed by 3093
Abstract
Acute exposure to high-dose ionizing irradiation has the potential to severely injure the hematopoietic system and its capacity to produce vital blood cells that innately serve to ward off infections and excessive bleeding. Developing a medical radiation countermeasure that can protect individuals from [...] Read more.
Acute exposure to high-dose ionizing irradiation has the potential to severely injure the hematopoietic system and its capacity to produce vital blood cells that innately serve to ward off infections and excessive bleeding. Developing a medical radiation countermeasure that can protect individuals from the damaging effects of irradiation remains a significant, unmet need and an area of great public health interest and concern. Despite significant advancements in the field of radiation countermeasure development to find a nontoxic and effective prophylactic agent for acute radiation syndrome, no such drug has yet been approved by the Food and Drug Administration. This study focuses on examining the metabolic corrections elicited by amifostine, a potent radioprotector, on tissues of vital body organs, such as the heart, spleen, and kidney. Our findings indicate that prophylaxis with this drug offers significant protection against potentially lethal radiation injury, in part, by correction of radiation-induced metabolic pathway perturbations. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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15 pages, 16697 KiB  
Article
Systemic Effects of Radiotherapy and Concurrent Chemo-Radiotherapy in Head and Neck Cancer Patients—Comparison of Serum Metabolome Profiles
by Karol Jelonek, Aleksandra Krzywon, Patrycja Jablonska, Ewa M. Slominska, Ryszard T. Smolenski, Joanna Polanska, Tomasz Rutkowski, Jolanta Mrochem-Kwarciak, Krzysztof Skladowski and Piotr Widlak
Metabolites 2020, 10(2), 60; https://doi.org/10.3390/metabo10020060 - 7 Feb 2020
Cited by 19 | Viewed by 3442
Abstract
Anticancer treatment induces systemic molecular changes that could be detected at the level of biofluids. Understanding how human metabolism is influenced by these treatments is crucial to predict the individual response and adjust personalized therapies. Here, we aimed to compare profiles of metabolites [...] Read more.
Anticancer treatment induces systemic molecular changes that could be detected at the level of biofluids. Understanding how human metabolism is influenced by these treatments is crucial to predict the individual response and adjust personalized therapies. Here, we aimed to compare profiles of metabolites in serum of head and neck cancer patients treated with concurrent chemo-radiotherapy, radiotherapy alone, or induction chemotherapy. Serum samples were analyzed by a targeted quantitative approach using combined direct flow injection and liquid chromatography coupled to tandem mass spectrometry, which allowed simultaneous quantification of 149 metabolites. There were 45 metabolites whose levels were significantly changed between pretreatment and within- or post-treatment serum samples, including 38 phospholipids. Concurrent chemo-radiotherapy induced faster and stronger effects than radiotherapy alone. On the other hand, chemotherapy alone did not result in significant changes. The decreased level of total phospholipids was the most apparent effect observed during the first step of the treatment. This corresponded to the loss of patients’ body mass, yet no correlation between both parameters was observed for individual patients. We concluded that different molecular changes were measured at the level of serum metabolome in response to different treatment modalities. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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Review

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28 pages, 396 KiB  
Review
Metabolomics in Radiation Biodosimetry: Current Approaches and Advances
by Merriline M. Satyamitra, David R. Cassatt, Brynn A. Hollingsworth, Paul W. Price, Carmen I. Rios, Lanyn P. Taliaferro, Thomas A. Winters and Andrea L. DiCarlo
Metabolites 2020, 10(8), 328; https://doi.org/10.3390/metabo10080328 - 11 Aug 2020
Cited by 21 | Viewed by 3750
Abstract
Triage and medical intervention strategies for unanticipated exposure during a radiation incident benefit from the early, rapid and accurate assessment of dose level. Radiation exposure results in complex and persistent molecular and cellular responses that ultimately alter the levels of many biological markers, [...] Read more.
Triage and medical intervention strategies for unanticipated exposure during a radiation incident benefit from the early, rapid and accurate assessment of dose level. Radiation exposure results in complex and persistent molecular and cellular responses that ultimately alter the levels of many biological markers, including the metabolomic phenotype. Metabolomics is an emerging field that promises the determination of radiation exposure by the qualitative and quantitative measurements of small molecules in a biological sample. This review highlights the current role of metabolomics in assessing radiation injury, as well as considerations for the diverse range of bioanalytical and sampling technologies that are being used to detect these changes. The authors also address the influence of the physiological status of an individual, the animal models studied, the technology and analysis employed in interrogating response to the radiation insult, and variables that factor into discovery and development of robust biomarker signatures. Furthermore, available databases for these studies have been reviewed, and existing regulatory guidance for metabolomics are discussed, with the ultimate goal of providing both context for this area of radiation research and the consideration of pathways for continued development. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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21 pages, 681 KiB  
Review
A Systematic Review of Metabolomic and Lipidomic Candidates for Biomarkers in Radiation Injury
by Elisabeth Vicente, Zeljko Vujaskovic and Isabel L. Jackson
Metabolites 2020, 10(6), 259; https://doi.org/10.3390/metabo10060259 - 20 Jun 2020
Cited by 23 | Viewed by 3396
Abstract
A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that [...] Read more.
A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that may be used in early phase testing to predict the course of the disease. Screening for biomarkers has recently extended to identify specific metabolomic and lipidomic responses to radiation using animal models. The objective of this review was to determine which metabolites or lipids most frequently experienced perturbations post-ionizing irradiation (IR) in preclinical studies using animal models of acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE). Upon review of approximately 65 manuscripts published in the peer-reviewed literature, the most frequently referenced metabolites showing clear changes in IR induced injury were found to be citrulline, citric acid, creatine, taurine, carnitine, xanthine, creatinine, hypoxanthine, uric acid, and threonine. Each metabolite was evaluated by specific study parameters to determine whether trends were in agreement across several studies. A select few show agreement across variable animal models, IR doses and timepoints, indicating that they may be ubiquitous and appropriate for use in diagnostic or prognostic biomarker panels. Full article
(This article belongs to the Special Issue Metabolomics/Lipidomics in Radiation Research)
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