Extracellular Vesicles in Modifying the Effects of Ionizing Radiation.

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.

[Defense Style Questionnaire (DSQ-40): factors, validity and reliability].

INTRODUCTION: Empirical research in defense mechanisms - a concept that stem from the work of Sigmund and Anna Freud and gave rise to a number of thematic approaches - dates back to the mid-20th century. From the psychometric measure instruments developed since that time, the present investigation was aimed to assess the short form of Defense Style Questionnaire that can be efficiently applied in clinical practice and that was supposed to be used as the sixth diagnostic factor of the new version of DSM. A multi-level validity analysis of DSQ-40 was carried out. METHODS: We applied trait assessing measures for anxiety, avoidant behavior, schizotypal traits and personality disorder diagnostic measures developed for DSM-5. To evaluate discriminant validity we applied instruments that assess the stability of self-esteem and the state of self and that can measure the clarity of self-representations. 670 healthy university students volunteered to participate in the investigation. RESULTS: Based on the applied questionnaires, it was revealed that its inner consistency and validity measures are adequate. Its factors that discriminate neurotic and immature defense styles can be applied to identify persons inclined to use either adaptive or maladaptive defense mechanisms. Our findings correspond to other international research results. CONCLUSION: Our results attest that DSQ-40 is a reliable instrument to assess defense style.

[Schizotypy Personality Questionnaire Brief Revisited (SPQ-BR) Hungarian adaptation and interpretation of factors].

INTRODUCTION: The purpose of the Schizotypy Personality Questionnaire - Brief Revised (SPQ-BR) is to help the diagnosis of schizotypial personality disorders within the framework of the DSM-5 and identification of people with an increased vulnerability towards schizophrenia related symptoms. The aim of our current study is twofold; validation of the SPQ-BR's Hungarian adaptation and investigating it's latent structure. METHODS: The sample consisted of 1702 Hungarian university students and university graduated persons. Exploratory factor analytic procedures were performed, cross-validating their results by the use if confirmatory factor analysis. RESULTS: The results suggested that the Hungarian SPQ-BR is best represented by a model of the hierarchical structure, reflected by seven first order factors, and two higher order dimensions of positive and negative symptoms. On lower order factors males were shown significantly greater constricted affects, and proneness to eccentric behaviors and unusual perceptions, while females were characterized by higher magical thinking, next to stronger social anxieties. Gender differences in the Ideas of references - Suspicion and odd speech scales were found to be non-significant. Concerning it''s validity with other scales we found that magical thinking and unusual perceptions from the positive symptoms significantly positively correlated with the magical ideation (MI), anxiousness (ASI), and self-concept clarity (SCCS) scales, next to a negative correlation between unusual perceptions and the self-esteem (RSES) scale. Among the negative symptoms the No close friends-Constricted affect and the Ideas of references - Suspicion subscales showed significant negative linear associations with the ASI, SCCS scales. CONCLUSION: The Hungarian version of the SPQ-BR showed adequate psychometrical properties, it was found to be reliable.

[MMPI-2 profiles in groups of systemic autoimmune disease - rheumatoid arthritis and systemic lupus erythematosus - patients]. / Szisztémás autoimmune betegek - rheumatoid arthritis és szisztémás lupus erythematosus - MMPI-2 profilijának vizsgálata.

OBJECTIVE: Systemic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are characterized by the alteration of immunological response, which can damage many organs and systems and result in a wide variety of clinical presentations. In addition to physical symptoms, psychiatric disorders are also common to many autoimmune diseases. Anxiety, depression, psychosis and cognitive deficits have the highest prevalence. The aim of this study was to display the degree of psychopathological symptoms in patients with RA and SLE. METHODS: Female inpatients with RA (N=68) and SLE (N=78) were recruited from the Rheumatology and Immunology Clinic of the University of Pecs and were asked to complete the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a short demografical form. The clinical personality profiles of the patient groups were explored and compared with each other. RESULTS: High scores (above 64T) were detected on the Hypochondriasis (Hs), Depression (D) and Hysteria (Hy) scales in both groups. Besides, the participants performed elevated scores on the Masculinity-Feminity (Mf), Psychasthenia (Pt) and Social Introversion (Si) clinical scales. They scored in the elevated range on the Physical Malfunctioning, Subjective Depression, Lassitude-Malaise and Somatic Complaints subscales of the neurotic triad. No significant difference was found on the ten clinical scales between the SLE and RA patients. CONCLUSION: Characteristics of MMPI-2 profiles in SLE and RA patients seem to be the consequence of the disease and a common feature of chronic conditions. High scores on the neurotic triad scales may reflect the comorbid psychiatric disorders and the somatic symptoms alike, so further investigations with the revised Hungarian MMPI-2 are needed.

Laying date and polygyny as determinants of annual reproductive success in male collared flycatchers (Ficedula albicollis): a long-term study.

Annual reproductive success (ARS) is one of the main components of lifetime reproductive success, a reliable measure of individual fitness. Previous studies often dealt with ARS and variables potentially affecting it. Among them, long-term studies that consider multiple factors at the same time are particularly important in understanding the adaptive value of different phenotypes. Here, we used an 18-year dataset to quantify the ARS of male collared flycatchers (Ficedula albicollis) on the basis of recruited offspring. We simultaneously assessed the effect of start of breeding, age, polygyny, body size and the expression of forehead patch (a sexually selected trait). The success of early breeding individuals was appreciably higher than late birds; however, breeding too early was also disadvantaged, and males that bred around the yearly median breeding date had the highest ARS. Polygynous males were more successful in years with good food supply, while in years with low food availability, they did not produce more recruits than monogamous males. The age of males, their forehead patch size and body size did not affect the number of recruits. Our findings support the importance of breeding date and suggest stabilizing selection on it in the long term. We also show that polygyny is not always advantageous for males, and its fitness pay-off may depend on environmental quality.

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project.

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).

Preliminary study of the exploration patients' experiences of chronic respiratory experiences during the COVID-19 pandemic using interpretative phenomenological analysis.

During the first period of coronavirus pandemic, respiratory patients may have been more vulnerable to mental health problems in addition to their physical vulnerability. The aim was to explore and deepen our understanding of the experiences of chronic respiratory patients at risk of pandemic COVID-19 using interpretative phenomenological analysis. The study involved 8 participants with asthma, COPD or cystic fibrosis. Three main themes emerged: 1. respiratory illness as a defining experience in everyday life, 2. the impact of the COVID-19 pandemic on the self and identity organisation, and 3. adaptation to experiencing vulnerability. Breathlessness as the most frightening feature of progressive lung disease, can be linked to fear and anxiety in different ways. The experience of vulnerability is a fundamental part of their lives. The potentially contagious nature of COVID-19 draws a sharp line between the endangered Self and the dangerous Other. In terms of their adaptation, we observe essentially self-defense mechanisms and emotion-focused strategies.

The role of the lived body during the integration of the traumatic experience of the sternotomy scar: A case study.

BACKGROUND: Open heart surgery is a potentially traumatic experience for patients, thus posing a real risk to both the patient's physical and mental health as well as bodily integrity. All of these can greatly affect the emotional relationship to the sternotomy scar, the physical aspect of self-representation. Sternotomy scars mark patients for life, yet our knowledge of patients' subjective experiences is unknown. METHOD: In our case study, we explore the embodied experiences of a woman (42) who underwent open heart surgery with the method of interpretative phenomenological analysis combined with drawings. RESULTS: The body and the bodily experiences play a prominent role in the formation, healing process, and symbolism of a scar. The central core of the traumatic experience of open heart surgery is the attack against the patient's sensation of bodily integrity. The interviewee experiences the surgery as abuse committed on her body, a memory that is deeply etched both in the physical memory and in the form of a scar on the skin. CONCLUSION: Based on our study, it seems that the corporeal dimension of posttraumatic growth may develop after the traumatic experience of heart surgery, in which bodily intimacy with oneself and Significant Others plays a major role. In this case study, the objective reality of the heart as "sick" flesh and the "broken, pierced" bone (Körper), as well as the dissociation-and then its integration-of the lived, living body experience (Leib) are outlined. Our case study was analysed in the theoretical framework of phenomenology and psychoanalysis.

Lifetime offspring production in relation to breeding lifespan, attractiveness, and mating status in male collared flycatchers.

As a comprehensive fitness parameter, lifetime reproductive success (LRS) is influenced by many different environmental and genetic factors, among which longevity is one of the most important. These factors can be reflected in secondary sexual characters, which may affect the life histories of individuals via social relations with conspecifics. Facultative polygyny in birds is another conspicuous reproductive trait that potentially increases male reproductive success, but lifetime success data in relation to polygyny are scarce. Here, we used 17 years of breeding data to quantify the LRS of male collared flycatchers (Ficedula albicollis) on the basis of lifetime recruitment of offspring. Breeding lifespan showed a positive relationship with LRS, and it was also significantly associated with mean recruitment of offspring per breeding year. Body size and sexually selected forehead patch size did not predict the number of recruits. Polygyny was positively associated with LRS, but when we corrected for lifespan, this relationship disappeared. Our results demonstrate that the relationship between longevity and LRS is not explained by the higher number of reproductive attempts when living longer, and question the adaptive value of polygyny in this population. The lack of association between forehead patch size and recruitment suggests that forehead patch is a poor indicator of phenotypic quality in our birds.

Measuring Immersion, Involvement, and Attention Focusing Tendencies in the Mediated Environment: The Applicability of the Immersive Tendencies Questionnaire.

This study explores the personal predispositions and dependencies while individuals use digital media and communication devices and analyses the statistical features of the Immersive Tendencies Questionnaire (ITQ) that is popular in assessing the personality trait-dependent reaction to mediated environments. The study evaluated 781 healthy graduates and postgraduates, of which 192 were men (average age: 28.6 years) and 589 were women (average age: 28.4 years). We applied several questionnaires to measure immersive tendencies in a mediated environment, adaptive and maladaptive personality predispositions, and problematic Internet use and Facebook addiction scales. We analyze the statistical features of the long and short forms of the Immersive Tendencies Questionnaire. The data obtained support the reliable usage of the short form of the instrument. The factor structure of the questionnaire presents dual facets. First, it indicates an absorptive and immersive tendency in any case of maladaptive tendencies. Second, it reflects an intensive capability to focus on the mediated environment with adequate cognitive control to avoid any contingency of being addicted. The short form of the ITQ is reliable and adequate to assess the relationship between the self-referred and environment-dependent psychological functions.

Factors influencing schizotypal personality trait-dependent immersion and digital media usage: Adaptation and maladaptation.

Immersion in the digital environment has been widely researched; however, the effects of adaptive and maladaptive schizotypal personality traits on immersion have received relatively little attention up till now. This study investigates the factors of personal immersion while using entertainment and digital communication applications and other variables such as problematic internet usage, and Facebook addiction. The Immersive Tendency Questionnaire was applied to measure participants' tendency to experience artistic and life-like scenarios in traditional settings (reading a book and watching a movie) and digital environments (playing computer games and using the internet). The study was conducted with 717 college students and graduate persons including, 186 males (mean age: 28.49) and 531 females (mean age: 28.4). The results show that lowered focusing abilities are directly linked with deficiencies in self-coherence, and maladaptive behavior that manifests in problematic internet and Facebook usage. Furthermore, the attention/focusing ability during immersion is accompanied by coherent self-structure and psychological well-being. Therefore, for people who have adequate focusing skills and coherent self-structure, the usage of social media and computer gaming can be considered adequate digital tools for developing their cognitive and social skills.

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow.

Ionizing radiation (IR)-induced bystander effects contribute to biological responses to radiation, and extracellular vesicles (EVs) play important roles in mediating these effects. In this study we investigated the role of bone marrow (BM)-derived EVs in the bystander transfer of radiation damage. Mice were irradiated with 0.1Gy, 0.25Gy and 2Gy, EVs were extracted from the BM supernatant 24 h or 3 months after irradiation and injected into bystander mice. Acute effects on directly irradiated or EV-treated mice were investigated after 4 and 24 h, while late effects were investigated 3 months after treatment. The acute effects of EVs on the hematopoietic stem and progenitor cell pools were similar to direct irradiation effects and persisted for up to 3 months, with the hematopoietic stem cells showing the strongest bystander responses. EVs isolated 3 months after irradiation elicited no bystander responses. The level of seven microRNAs (miR-33a-3p, miR-140-3p, miR-152-3p, miR-199a-5p, miR-200c-5p, miR-375-3p and miR-669o-5p) was altered in the EVs isolated 24 hour but not 3 months after irradiation. They regulated pathways highly relevant for the cellular response to IR, indicating their role in EV-mediated bystander responses. In conclusion, we showed that only EVs from an early stage of radiation damage could transmit IR-induced bystander effects.

Investigation of lifestyle difficulties in dialysis patients using quantitative testing methods / Dializált betegek életviteli nehézségeinek megismerése kvantitatív vizsgálómódszerekkel.

Összefoglaló. Bevezetés: A krónikus vesebetegség tünetei, a kezelés sajátosságai nagymértékben korlátozzák a páciensek mindennapi életvitelét, hatással vannak testi és lelki egészségükre, és nehezítik társas kapcsolataikat. Célkituzések: A jelen kutatás célja a magyar dializált betegpopuláció egészségmuveltségének, életminoségének és betegségterhének megismerése, továbbá a kezelési típusok hatását kívántuk felmérni a fent említett pszichológiai tényezok mentén. Módszer: A vizsgálatban 42 krónikus dializált személy vett részt: 31 hemodializált és 11 hasi dialízist végzo vesebeteg. Átlagéletkoruk 63,33 ± 12,92 év. A minta életkor, nemi eloszlás és családi állapot alapján reprezentatív. Kérdoíves technikával mértük a betegek életminoségét, egészségmuveltségét és betegségterhét. Eredmények: Eredményeink szerint a peritonealis dialízist végzo betegek szignifikánsan magasabb egészségmuveltséggel rendelkeznek, mint hemodializált betegtársaik. Ez a jelentos különbség az életminoségük több területén is kimutatható volt. Következtetés: Eredményeink a betegedukáció és a kezeloszemélyzettol kapott támogatás (bátorítás) jelentoségére hívják fel a figyelmet. A betegoktatás a hemodializált betegcsoport esetében is kiemelten fontos. A klinikai szempontból hasznos intervenciós javaslatokat fogalmaztunk meg, melyek célzottan az egészségmuveltség fejlesztésére irányulnak. Orv Hetil. 2021; 162(30): 1208-1215. INTRODUCTION: The symptoms of chronic kidney disease, the peculiarities of the treatment greatly limit the patients' daily life, affect their physical and mental health and make their social relationships more difficult. OBJECTIVE: The purpose of this research is to explore the health literacy, the health-related quality of life and illness intrusiveness of Hungarian dialysis patients. Furthermore, we wanted to assess the effect of treatment types along the psychological factors mentioned above. METHOD: The sample consisted of 42 patients with chronic kidney disease, 31 of whom have hemodialysis and 11 have peritoneal dialysis treatment. Their mean age was 63.33 ±12.92 years. The sample is representative by age, gender, and marital status. We measured the health-related quality of life, the health literacy and illness intrusiveness of the patients using special questionnaire techniques. RESULTS: The peritoneal dialysis patients have significantly higher health literacy than their hemodialysis counterparts. This significant difference was seen in several areas of their quality of life as well. CONCLUSION: Our results draw attention to the importance of patient education and the special support by the treatment staff. The patient education for the haemodialysis group is of paramount importance for the hemodialysis group, too. We have formulated clinically useful intervention proposals aimed at improving health literacy. Orv Hetil. 2021; 162(30): 1208-1215.

Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect.

Radiation-induced bystander effect is a biological response in nonirradiated cells receiving signals from cells exposed to ionising radiation. The aim of this in vivo study was to analyse whether extracellular vesicles (EVs) originating from irradiated mice could induce modifications in the redox status and expression of radiation-response genes in bystander mice. C57BL/6 mice were whole-body irradiated with 0.1-Gy and 2-Gy X-rays, and EVs originating from mice irradiated with the same doses were injected into naïve, bystander mice. Lipid peroxidation in the spleen and plasma reactive oxygen metabolite (ROM) levels increased 24 h after irradiation with 2 Gy. The expression of antioxidant enzyme genes and inducible nitric oxide synthase 2 (iNOS2) decreased, while cell cycle arrest-, senescence- and apoptosis-related genes were upregulated after irradiation with 2 Gy. In bystander mice, no significant alterations were observed in lipid peroxidation or in the expression of genes connected to cell cycle arrest, senescence and apoptosis. However, there was a systemic increase in the circulating ROM level after an intravenous EV injection, and EVs originating from 2-Gy-irradiated mice caused a reduced expression of antioxidant enzyme genes and iNOS2 in bystander mice. In conclusion, we showed that ionising radiation-induced alterations in the cellular antioxidant system can be transmitted in vivo in a bystander manner through EVs originating from directly irradiated animals.

Cognitive Gain or Handicap: Magical Ideation and Self-Absorption in Clinical and Non-clinical Participants.

Background: This study aimed to examine magical ideation and absorption traits across non-clinical and clinical groups to determine their potential adaptive and maladaptive functions. Method: We enrolled 760 healthy participants from neighboring communities (female = 53.2%). Moreover, we recruited 318 patients (female = 66.5%), which included 25, 183, and 110 patients with schizophrenia spectrum disorders, anxiety disorders, and mood disorders, respectively. Potentially adaptive and maladaptive sociocognitive functions were measured to determine the role of magical ideation and self-absorption in patients with psychiatric disorders. Results: The degree of magical ideation and absorption gradually increased in the following order: anxiety disorders, mood disorders, and schizophrenia spectrum disorders. Furthermore, enhanced self-absorption-related enhanced consciousness traits were essential indicators of the presence of self-integration weakness in patients with schizophrenia spectrum disorders. Conclusion: Magical ideation and psychological absorption may be considered as mental model construction functions, which result in both gains and handicaps in social adaptation.

Sequential organization of birdsong: relationships with individual quality and fitness.

Many vocalizing animals produce the discrete elements of their acoustic signals in a specific sequential order, but we know little about the biological relevance of this ordering. For that, we must characterize the degree by which individuals differ in how they organize their signals sequentially and relate these differences to variation in quality and fitness. In this study, we fulfilled these tasks in male collared flycatchers (Ficedula albicollis). We characterized the sequential order of syllables with a network analysis approach and studied the consistency of network variables on distinct time scales (within day, between days, and between years), and assessed their relationship with such quality indicators like age, body condition, arrival date, and fitness related proxies like survival to the next year and pairing success. We found that the syllables were associated nonrandomly with one another and both the frequency differences of consecutive syllables and the number of motif types were higher in the original than in randomized syllable sequences. Average degree and small-worldness showed considerable among-individual differences and decreasing repeatability with increasing time scale. Furthermore, we found relationships between male age and average degree among and within individuals. Accordingly, older males produce syllable sequences by using common syllables less often than younger individuals. However, the network variables showed no relationship with fitness-related variables. In conclusion, the sequential organization of birdsong has the potential to encode individual-specific characteristics, which thus could be used as signal in social interactions and thus potentially could be subject to sexual selection.

RENEB/EURADOS field exercise 2019: robust dose estimation under outdoor conditions based on the dicentric chromosome assay.

PURPOSE: Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. MATERIALS AND METHODS: For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS: The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS: The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles.

OBJECTIVES: Ionising radiation-induced alterations affecting intercellular communication in the bone marrow (BM) contribute to the development of haematological pathologies. Extracellular vesicles (EVs), which are membrane-coated particles released by cells, have important roles in intercellular signalling in the BM. Our objective was to investigate the effects of ionising radiation on the phenotype of BM-derived EVs of total-body irradiated mice. METHODS: CBA mice were irradiated with 0.1 Gy or 3 Gy X-rays. BM was isolated from the femur and tibia 24 h after irradiation. EVs were isolated from the BM supernatant. The phenotype of BM cells and EVs was analysed by flow cytometry. RESULTS: The mean size of BM-derived EVs was below 300 nm and was not altered by ionising radiation. Their phenotype was very heterogeneous with EVs carrying either CD29 or CD44 integrins representing the major fraction. High-dose ionising radiation induced a strong rearrangement in the pool of BM-derived EVs which were markedly different from BM cell pool changes. The proportion of CD29 and CD44 integrin-harbouring EVs significantly decreased and the relative proportion of EVs with haematopoietic stem cell or lymphoid progenitor markers increased. Low-dose irradiation had limited effect on EV secretion. CONCLUSIONS: Ionising radiation induced selective changes in the secretion of EVs by the different BM cell subpopulations. ADVANCES IN KNOWLEDGE: The novelty of the paper consists of performing a detailed phenotyping of BM-derived EVs after in vivo irradiation of mice.

Mitochondrial DNA damage in the hair bulb: can it be used as a noninvasive biomarker of local exposure to low LET ionizing radiation?

Purpose: Our aim was to evaluate whether mitochondrial DNA (mtDNA) damage in hair bulbs could be a suitable biomarker for the detection of local exposure to ionizing radiation.Materials and methods: Mouse hair was collected 4 and 24 hours, 3 and 10 days after single whole-body exposure to 0, 0.1, and 2 Gy radiation. Pubic hair (treated area) and scalp hair (control area) were collected from 13 prostate cancer patients before and after fractioned radiotherapy with an average total dose of 2.7 Gy to follicles after five fractions. Unspecified lesion frequency of mtDNA was analyzed with long PCR, large mtDNA deletion levels were tested with real-time PCR.Results: Unspecified lesion frequency of mtDNA significantly increased in mouse hair 24 hours after irradiation with 2 Gy, but variance among samples was high. No increase in lesion frequency could be detected after 0.1 Gy irradiation. In prostate cancer patients, there was no significant change in either the unspecified lesion frequency or in the proportion of 4934-bp deleted mtDNA in pubic hair after radiotherapy. The proportions of murine 3860-bp common deletion, human 4977-bp common deletion and 7455-bp deleted mtDNA were too low to be analyzed reliably.Conclusions: Our results suggest that the unspecified lesion frequency and proportion of large deletions of mtDNA in hair bulbs are not suitable biomarkers of exposure to ionizing radiation.

Extracellular vesicles mediate low dose ionizing radiation-induced immune and inflammatory responses in the blood.

PURPOSE: Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on plasma EV miRNA profiles. MATERIALS AND METHODS: C57Bl/6 mice were total-body irradiated with 0.1 and 2 Gy, bone marrow-derived EVs were isolated, and injected systemically into naive, 'bystander' animals. Proteome profiler antibody array membranes were used to detect alterations in plasma, both in directly irradiated and bystander mice. MiRNA profile of plasma EVs was determined by PCR array. RESULTS: M-CSF and pentraxin-3 levels were increased in the blood of directly irradiated and bystander mice both after low and high dose irradiations, CXCL16 and lipocalin-2 increased after 2 Gy in directly irradiated and bystander mice, CCL5 and CCL11 changed in bystander mice only. Substantial overlap was found in the cellular pathways regulated by those miRNAs whose level were altered in EVs isolated from the plasma of mice irradiated with 0.1 and 2 Gy. Several of these pathways have already been associated with bystander responses. CONCLUSION: Low and high dose effects overlapped both in EV-mediated alterations in signaling pathways leading to RIBE and in their systemic manifestations.