Varied Photon Radiation Sources Produce Differences in Cellular Response.

In vitro studies allow evaluation of normal or cancer cell responses to radiation, either alone or in combination with agents used to modify these biological responses. Ionizing radiation can be produced by a variety of particles and sources, with varying energy spectra, interaction probabilities, linear energy transfer, dose uniformity, dose rates, and delivery methods. Multiple radiation sources have been used to irradiate cells in the published literature. However, the equivalence of response in cell culture models across radiation sources has not been rigorously established. Moreover, current reporting of radiation source parameters lacks consistency and rigor which may impact the reproducibility of pre-clinical data between laboratories. Relevant choices of radiation source are also of high importance due to growing interest in comparing photon versus particle radiation effect on biological responses. Therefore, this study robustly evaluates the cellular response (cell survival, apoptosis, and DNA damage) of three distinct cell lines using four unique photon generating radiation sources. We hypothesize there may be subtle differences across the radiation sources, without an appreciable difference in cellular response. The four photon irradiation energies investigated, 662 keV, 100 kVp, 220 kVp, 6 MV, did produce subtle differences in DNA damage and cell survival when treating three distinct tumor cell lines. These variations in cellular response emphasize the need to carefully consider irradiation source, energy, and dose rate depending on study goal and endpoint.

El ocaso del modelo lineal sin umbral / The downfall of the linear non-threshold model

El modelo lineal sin umbral (MLSU) es una función dosis-respuesta teórica obtenida de extrapolar los efectos tardíos debidos a la exposición a altas dosis de radiación ionizante al rango de las bajas dosis, pero existen grandes incertidumbres respecto a su validez. La aceptación del MLSU como modelo probabilístico preponderante ha sobrevivido hasta nuestros días y constituye la piedra angular que sostiene las políticas actuales de protección radiológica. En las últimas décadas, los avances en biología molecular y evolutiva, en la inmunología del cáncer, así como los resultados obtenidos de los estudios epidemiológicos y en modelos animales, han puesto en entredicho la fiabilidad del MLSU en favor de otras alternativas, como la teoría hormética. A la vista de las evidencias, se hace necesario un debate entre las sociedades científicas implicadas y los organismos reguladores que aborde una redefinición de las bases de la protección radiológica, cuya importancia sería capital en el ámbito médico

The linear non-threshold model (LNTM) is a theoretical dose-response function as a result of extrapolating the late effects of high-dose exposure to ionizing radiation to the low-dose range, but there is great uncertainty about its validity. The acceptance of LNTM as the dominant probabilistic model have survived to the present day and it is actually the cornerstone of current radiation protection policies. In the last decades, advances in molecular and evolutive biology, cancer immunology, and many epidemiological and animal studies have cast serious doubts about the reliability of the NLTM, as well as suggesting alternative models, like the hormetic theory. Considering the given evidences, a discussion between the involved scientific societies and the regulatory commissions is promtly required in order to to reach a redefiniton of theradiation protection basis, as it would be specially crucial in the medical field

Efeitos da radioterapia na obtenção da osseointegração em ratos / Effects of radiotherapy in obtaining osseointegration in rats

A radioterapia é o uso da aplicação de radiação ionizante em áreas específicas, visando tratamento de tumores. Porém, a área irradiada e os tecidos normais circundantes estão sujeitos a danos agudos e crônicos. As injúrias no tecido ósseo variam desde osteopenia até osteorradionecrose e, devido a estas alterações, pacientes irradiados portadores de implantes vêm demonstrando maior taxa de insucesso. O objetivo deste estudo foi avaliar os efeitos da radioterapia, simulando uma dose total de um tratamento radioterápico convencional para pacientes oncológicos, na neoformação óssea e na osseointegração de implantes em fêmures de ratos. Foram utilizados neste estudo 66 ratos que receberam implantes cilíndricos de titânio comercialmente puro (TiCp) nos fêmures direito e esquerdo. Os animais foram divididos em 3 grupos: a) Grupo controle (C): cirurgia de colocação dos implantes (tecido sadio sem irradiação); b) Grupo irradiação precoce (Ip): cirurgia de colocação dos implantes seguido de irradiação após 24h; c) Grupo irradiado (I): irradiação e após 4 semanas, cirurgia de colocação dos implantes. Os animais dos grupos Ip e I foram submetidos a irradiação em 02 sessões de 15 Gy, totalizando a dose de 30 Gy. Os animais foram eutanasiados nos períodos de 2 e 7 semanas após o tratamento. Durante o experimento, os animais foram cuidadosamente monitorados quanto as alterações clínicas. Em cada período, 06 animais foram submetidos à análise histomorfométrica, visando avaliar a neoformação óssea e a interface osso-implante. Os outros 05 animais, dos períodos de 2 e 7 semanas após o tratamento, foram submetidos ao teste de torque reverso para avaliar a força de fixação osso-implante, obtida na osseointegração. Todos os dados foram estatisticamente analisados por meio da análise de variância de 2 fatores para torque reverso, porcentagem de área de formação óssea (BAFO) e porcentagem de superfície de contato osso implante (BIC) com nível de significância a 5%. O teste de Tukey foi realizado para determinação dos grupos homogêneos. A irradiação ionizante influenciou negativamente de maneira estatisticamente significante, retardando o processo de osseointegração, porém, não sendo capaz de inibí-lo(AU)

The radiotherapy is ionizing radiation proceeding in specific areas, aiming at the treatment of tumors. However, the irradiated area and the surrounding normal tissue can develop acute and chronic damage. In bone tissue, injuries ranging from osteopenia to osteroadionecrosis and due to these changes patients irradiated with implants have shown higher failure rate. The objective of this study was to evaluate the effects of radiation, simulating a total dose of a conventional radiotherapy treatment for cancer, bone regeneration and osseointegration of implants in femurs of rats. It was used in this study 66 mice that receive cylindrical implants of commercially pure titanium (cpTi) on the right and left femurs. The animals were divided into 3 groups: a) control group (C): implant placement surgery (control group - healthy tissue without irradiation); b) Group early irradiation (Ip): placement of implants surgery followed by radiation after 24h; c) Group irradiated (I): irradiation and after 4 weeks of surgery implant placement. The animals of the Ip and I groups were subjected to irradiation in a double step at a dose of 15 Gy each, totalizing dose of 30 Gy. The animals were euthanized at periods of 2 and 7 weeks after treatment. During the experiment, the animals were carefully monitored for clinical changes. In each period 06 animals were submitted to histomorphometric analysis, to evaluate the bone formation and bone-implant interface. The other 05 animals, in periods of 2 and 7 weeks after treatment, were submitted to the reverse switch test to evaluate the strength of bone-implant fixation, obtained in osseointegration. All data were statistically analyzed by means of the 2-factor variance analysis for reverse torque, percentage of bone area fraction occupancy (BAFO) and percentage of bone implant contact (BIC) with significance level at 5%. The Tukey test was performed to determine the homogeneous groups. The ionizing radiation influenced negatively in a statistically significant way, delaying the process of osseointegration, but not being able to inhibit it(AU)

Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival.

During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight.

Mieloma múltiple en neuroradiólogo vascular intervencionista: ¿Enfermedad profesional? / Multiple myeloma in a vascular and interventional neuroradiologist: Occupational disease?

Varón de 59 años, neuroradiólogo vascular intervencionista con una antigüedad laboral de 35 años. Sin antecedentes patológicos de interés. Asintomático hasta enero de 2015 que inicia dorsalgia súbita tras sobresfuerzo. Acude a consulta de salud laboral con el diagnóstico de mieloma múltiple. Solicita informe para la determinación de la contingencia como enfermedad profesional. Investigamos el caso revisando los efectos biológicos de las radiaciones ionizantes (deterministas y estocásticos), el cuadro de enfermedades profesionales provocadas por radiaciones ionizantes (grupo 2 y 6) y haciendo una profunda búsqueda bibliográfica acerca de los trastornos hematopoyéticos y la exposición a radiaciones ionizantes. Finalmente apoyamos la determinación de enfermedad profesional (AU)

A 59 years-old 4male, vascular and interventional neuroradiologist with 35 years of seniority.Without pathological backgrounds of interest. Asymptomatic until January 2015 when he starts with sudden dorsalgia after muscular effort. Attends to consultation of occupational health service with the diagnosis of Multiple Myeloma. He seeks for determination of occupational contingency. We researched the case checking for the biological effects of the ionizing radiations (deterministic and stochastic effects), the occupational disease chart caused by ionozing radiations (group 2 and 6) and making an exhaustive bibliographical search of the hematopoietic disorders and the exposition to ionizing radiations. Finally we support the determination of occupational contingency (AU)

Carcinoma de mama en trabajadora expuesta a radiaciones ionizantes / Female Worker with breast cacinoma exposed to ionizing radiation

M.A., de 40 años de edad, es técnico especialista de radiodiagnóstico del hospital. Es una trabajadora profesionalmente expuesta a radiaciones ionizantes categoría A. Es diagnosticada de carcinoma ductal infiltrante de mama derecha. Tratamiento: tumorectomía, quimioterapia (Taxotere), Radioterapia con acelerador lineal (50 Grays) y braquiterapia con Iridio-192 (8 Grays). A los 18 meses es alta médica y acude a la consulta de Medicina del Trabajo para examen de salud tras ausencia por larga enfermedad. Consultado el Cuadro de Enfermedades Profesionales (Real Decreto 1299/2006) y el Protocolo de vigilancia sanitaria específica para radiaciones ionizantes del Ministerio de Sanidad, no aportan información útil para definir los criterios de aptitud. Se revisa historia clínica de la paciente y bibliografía y se concluye: la trabajadora es calificada APTA para el puesto de trabajo de técnico especialista de radiodiagnóstico (AU)

M.A., female, 40 years old, technical specialist hospital radiology, diagnosed with invasive ductal carcinoma of the right breast. She is a worker professionally exposed to ionizing radiation A. Medical treatment: Lumpectomy, chemotherapy (Taxotere), radiotherapy linear accelerator (50 Grays) and brachytherapy with Iridium-192 (8 Grays). After 18 months treatment, she is medically discharged and attended to the Occupational Health consultation for a health checking, after a long absence due to her illness. The Retrieved Table of Occupational Diseases (Royal Decree 1299/2006) and Specific Health Surveillance Protocol for Ionizing Radiation (Health Ministry) consulted, any useful information has been provided to define aptness criteria. Once the bibliography and the patient’s clinical history reviewed, our conclusion was that the worker was SUITABLY qualified to carry out with her x-ray technical job (AU)