How does radiation kill cells?

Recent advances in the understanding of intracellular signaling after genotoxic injury have led to a better understanding of the pathways that influence radiation-induced cell death. Particular progress has been made in defining molecular controls of apoptosis and radiation-induced cell cycle arrest, as well as the possible role of telomerase activity in stabilizing DNA breaks.     

The ecology of a continental evolutionary radiation: Is the radiation of sigmodontine rodents adaptive?

Evolutionary radiations on continents are less well‐understood and appreciated than those occurring on islands. The extent of ecological influence on species divergence can be evaluated to determine whether a radiation was ultimately the outcome of divergent natural selection or else arose mainly by nonecological divergence. Here, we used phylogenetic comparative methods to test distinct hypotheses corresponding to adaptive and nonadaptive evolutionary scenarios for the morphological evolution of sigmodontine rodents. Results showed that ecological variables (diet and life‐mode) explain little of the shape and size variation of sigmodontine skulls and mandibles. A Brownian model with varying rates for insectivory versus all other diets was the most likely evolutionary model. The insectivorous sigmodontines have a faster rate of morphological evolution than mice feeding on other diets, possibly due to stronger selection for features that aid insectivory. We also demonstrate that rapid early‐lineage diversification is not accompanied by high morphological divergence among subclades, contrasting with island results. The geographic size of continents permits spatial segregation to a greater extent than on islands, allowing for allopatric distributions and escape from interspecific competition. We suggest that continental radiations of rodents are likely to produce a pattern of high species diversification coupled with a low degree of phenotypic specialization.     

Propagation of electromagnetic radiation in mitochondria?

Infanticide by primate males was considered rare if groups contain more than one adult male because, owing to lower paternity certainty, a male should be less likely to benefit from infanticide. Guided by recent evidence for strong variation of infanticide in primate multi-male groups, we modelled the conditions for when infanticide should occur for a group with a resident and an immigrant male. Setting the parameters (e.g. infant mortality, reduction of interbirth interval, life-time reproductive success, genetic representation) to fit the conditions most commonly found in nature, we develop a game-theoretic model to explore the influence of age and dominance on the occurrence of infanticide and infant defence. Male age strongly impacts the likelihood of an attack which is modified by the father's defence. If the new male is dominant he is likely to attack under most circumstances whereas a subordinate male will only attack if the father does not defend. These model scenarios fit the conditions under which infanticide is known to occur in primate multi-male groups and offer an explanation why infanticide is common in some multi-male groups and rare in others. Overall, the benefits for infanticidal males are strongly governed by a reduced interbirth interval while advantages via improved genetic representation in the gene pool contribute but a minor fraction.     

What is a 'low dose' of radiation?

Although the expression of radiation-induced biological effects and responses may be at either the cell, organ or organism level, induction of some of these phenomena (e.g. cancer of clastogenic and genetic effects) can have their origin in the interaction of a single charged particle with the target-containing volume (TCV) of the cell, e.g. the cell nucleus. However, the independent variable now used in both organ and cell population studies, the absorbed dose to the organ, provides no information directly on particle-TCV interactions. Even if calculated as a mean to an organized population of cells, the absorbed dose becomes a composite and confounded quantity, (FzN), in which F is the fraction of TCVs 'hit' by a particle during a given exposure, z is the mean value of z1, the energy absorbed in the TCV in a single hit, and N is the mean number of hits per affected TCV. Scientific precepts demand the avoidance of such confounded variables by achieving their isolation. The needed separation can be effected by the use of microdosimetric techniques, which make it possible to hold one component quantity constant while the others are varied. As an example, low-level radiation exposure (LLE) can be used to hold F at a constant value of 0.2 where, on average, there is but one hit per TCV. The probability of a cellular quantal response, as a function of z1 only, can then be determined by use of LLE to radiations covering a wide span of LETs. Conversely, the effect of varying only the fraction of cells hit can be studied by holding z constant. This can be accomplished by working within a narrow band of LET, but only in the LLE range. The effectiveness of preirradiation altering cell sensitivity as a function of the number of hits per TCV can be determined by working within, and somewhat above, the LLE range. In either risk assessment or the application of radiation as a pretreatment, minimal consequences can be assured only if very low-level exposure is employed in order that F will be small, and if the exposure is in a field of radiation of very low LET so that z1 will be as small as possible. That is to say, exposure conditions with low consequences cannot be specified in terms of any single quantity.     

Low-dose radiation exposure and atherosclerosis in ApoE⁻/⁻ mice

The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE?/?). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate.     

Smartphones and tablets: Reshaping radiation oncologists’ lives

BackgroundSmartphones and tablets are new handheld devices always connected to an information source and capable of providing instant updates, they allow doctors to access the most updated information and provide decision support at the point of care.AimThe practice of radiation oncology has always been a discipline that relies on advanced technology. Smartphones provide substantial processing power, incorporating innovative user interfaces and applications.Materials and methodsThe most popular smartphone and tablet app stores were searched for “radiation oncology” and “oncology” related apps. A web search was also performed searching for smartphones, tablets, oncology, radiology and radiation oncology.ResultsSmartphones and tablets allow rapid access to information in the form of podcasts, apps, protocols, reference texts, recent research and more.ConclusionWith the rapidly changing advances in radiation oncology, the trend toward accessing resources via smartphones and tablets will only increase, future will show if this technology will improve clinical care.     

Does reduced gravity alter cellular response to ionizing radiation?

This review addresses the purported interplay between actual or simulated weightlessness and cellular response to ionizing radiation. Although weightlessness is known to alter several cellular functions and to affect signaling pathways implicated in cell proliferation, differentiation and death, its influence on cellular radiosensitivity has so far proven elusive. Renewed controversy as to whether reduced gravity enhances long-term radiation risk is fueled by recently published data that claim either overall enhancement of genomic damage or no increase of radiation-induced clastogenicity by modeled microgravity in irradiated human cells. In elucidating this crucial aspect of space radiation protection, ground-based experiments, such as those based on rotating-wall bioreactors, will increasingly be used and represent a more reproducible alternative to in-flight experiments. These low-shear vessels also make three-dimensional cellular co-cultures possible and thus allow to study the gravisensitivity of radioresponse in a context that better mimics cell-to-cell communication and hence in vivo cellular behavior.     

Can angiotensin-converting enzyme inhibitors protect against symptomatic radiation pneumonitis?

This study was designed to determine whether patients taking angiotensin-converting enzyme (ACE) inhibitors while receiving radiation therapy for lung cancer are protected from developing symptomatic radiation pneumonitis. The records of 213 eligible patients receiving thoracic irradiation for lung cancer with curative intent at Duke University Medical Center from 1994-1997 were reviewed. Of the 213 patients, 26 (12.2%) were on ACE inhibitors (usually for the management of hypertension) during radiotherapy (group 1); the remaining 187 patients (group 2) were not. Patients were irradiated, with fields shaped to protect normal tissues, with total doses of 50-80 Gy. After treatment, patients were generally followed every 3 months for 2 years, then every 6 months thereafter. Symptomatic radiation pneumonitis was scored according to modified National Cancer Institute Common Toxicity Criteria (i.e., radiographic changes alone were not sufficient for the diagnosis of pneumonitis). There was no difference in the incidence of pneumonitis between the two groups (P = 0.75). Fifteen percent of the patients on ACE inhibitors (group 1) developed symptomatic radiation-induced lung injury compared to 12% of the patients not receiving these drugs (group 2). Although patients in group 1 tended to develop pneumonitis slightly sooner than did patients in group 2, this difference also was not significant (P = 0. 8). Within the dose range prescribed for treating hypertension, ACE inhibitors do not appear to either decrease the incidence or delay the onset of symptomatic radiation pneumonitis among lung cancer patients receiving thoracic irradiation.     

Why is Deinococcus radiodurans so resistant to ionizing radiation?

When exponential-phase cultures of Deinococcus radiodurans are exposed to a 5000-Gray dose of gamma radiation, individual cells suffer massive DNA damage. Despite this insult to their genetic integrity, these cells survive without loss of viability or evidence of mutation, repairing the damage by as-yet-poorly-understood mechanisms.     

Marine gregarines: evolutionary prelude to the apicomplexan radiation?

Gregarine apicomplexans inhabit the intestines, coeloms and reproductive vesicles of invertebrates. An emphasis on specific ancestral characteristics in marine gregarines has given the group a reputation of being 'primitive.' Although some lineages have retained characteristics inferred to be ancestral for the group, and perhaps apicomplexans as a whole, most gregarines represent highly derived parasites with novel ultrastructural and behavioral adaptations. Many marine gregarines have become giants among single-celled organisms and have evolved ornate surface structures. A comparison of gregarine morphology, placed in a modern phylogenetic context, helps clarify the earliest stages of apicomplexan evolution, the origin of Cryptosporidium, and specific cases of convergent evolution within the group and beyond.     

Tissue TGF-β expression following conventional radiotherapy and pulsed low-dose-rate radiation

The release of inflammatory cytokines has been implicated in the toxicity of conventional radiotherapy (CRT). Transforming growth factor β (TGF-β) has been suggested to be a risk marker for pulmonary toxicity following radiotherapy. Pulsed low-dose rate radiotherapy (PLDR) is a technique that involves spreading out a conventional radiotherapy dose into short pulses of dose with breaks in between to reduce toxicities. We hypothesized that the more tolerable toxicity profile of PLDR compared with CRT may be related to differential expression of inflammatory cytokines such as TGF-β in normal tissues. To address this, we analyzed tissues from mice that had been subjected to lethal doses of CRT and PLDR by histology and immunohistochemistry (IHC). Equivalent physical doses of CRT triggered more cellular atrophy in the bone marrow, intestine, and pancreas when compared with PLDR as indicated by hematoxylin and eosin staining. IHC data indicates that TGF-β expression is increased in the bone marrow, intestine, and lungs of mice subjected to CRT as compared with tissues from mice subjected to PLDR. Our in vivo data suggest that differential expression of inflammatory cytokines such as TGF-β may play a role in the more favorable normal tissue late response following treatment with PLDR.     

Low-dose total-body γ irradiation modulates immune response to acute proton radiation

Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ??Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.     

Is UV-B radiation affecting charophycean algae in shallow freshwater systems?

The objective of this study was to determine the effects of UV-B radiation on charophycean algae under natural conditions, since charophytes enhance water transparency in freshwater systems and levels of UV-B radiation have increased by ozone depletion. Potential and actual UV-B effects were studied by combining a glasshouse experiment in which plants were exposed to various levels of UV-B radiation and field measurements in two freshwater systems dominated by charophytes in the Netherlands. The glasshouse experiment showed that charophytes were sensitive to UV-B radiation. UV-B radiation negatively affected growth, while it increased levels of DNA damage in Chara aspera. Moreover, the charophytes did not seem to develop UV-B screens to protect against UV-B radiation since no increase in UV-B absorbing compounds was found. At field conditions, both spectroradiometrical measurements and DNA dosimeters showed that UV-B radiation was attenuated quickly in both freshwater systems, indicating that UV-B does not reach the submerged charophyte vegetation. However, specific conditions, like fluctuating water tables, may result in UV-B exposure to charophytes for certain periods annually.     

Effect of γ radiation on physiological parameters of the ethanolic fermentation

This work examines the efficacy of radiation in reducing the viability of certain contaminating bacteria of sugar-cane must and the consequential beneficial effect of lethal doses of radiation on some physiological parameters of the yeast-based ethanolic fermentation. The must from sugar-cane juice was inoculated with different bacteria that usually contaminate the must in the production facilities: Bacillus and Lactobacillus. The contaminated must was irradiated at 2.0, 4.0, 6.0, 8.0 and 10.0 kGy of gamma radiation. The population density of the bacteria in the irradiated must was recorded. Ethanolic fermentation by yeast (Saccharomyces cerevisiae) was carried out and the total acidity, the volatile acidity and the organic acids (lactic and acetic) produced during the fermentation were determined. The ethanol yield was also recorded. The treatment with radiation reduced the population of the contaminating microorganisms of the sugar-cane must. The acidity and the organic acids (lactic and acetic) produced during the fermentation decreased as the dose of radiation applied to the must increased. It is concluded that irradiation was efficient in decontaminating the sugar-cane must and improved the biochemical parameters of the ethanolic fermentation, including the ethanol yield by 2%.     

Role of Purα in the cellular response to ultraviolet-C radiation

Purα is a nucleic acid-binding protein with DNA-unwinding activity, which has recently been shown to have a role in the cellular response to DNA damage. We have investigated the function of Purα in Ultraviolet-C (UVC) radiation-induced DNA damage and nucleotide excision repair (NER). Mouse embryo fibroblasts from PURA^-/- knockout mice, which lack Purα, showed enhanced sensitivity to UVC irradiation as assessed by assays for cell viability and clonogenicity compared to Purα positive control cultures. In reporter plasmid reactivation assays to measure the removal of DNA adducts induced in vitro by UVC, the Purα-negative cells were less efficient in DNA damage repair. Purα-negative cells were also more sensitive to UVC-induced DNA damage measured by Comet assay and showed a decreased ability to remove UVC-induced cyclobutane pyrimidine dimers. In wild-type mouse fibroblasts, expression of Purα is induced following S-phase checkpoint activation by UVC in a similar manner to the NER factor TFIIH. Moreover, co-immunoprecipitation experiments showed that Purα physically associates with TFIIH. Thus, Purα has a role in NER and the repair of UVC-induced DNA damage.Key words: purα, ultraviolet radiation, DNA damage, DNA repair, nucleotide excision repair, TFIIH     

Evidence for a Müllerian mimetic radiation in Asian pitvipers

Müllerian mimicry, in which toxic species gain mutual protection from shared warning signals, is poorly understood in vertebrates, reflecting a paucity of examples. Indirect evidence for mimicry is found if monophyletic species or clades show parallel geographic variation in warning patterns. Here, we evaluate a hypothesis of Müllerian mimicry for the pitvipers in Southeast Asia using a phylogeny derived from DNA sequences from four combined mitochondrial regions. Mantel matrix correlation tests show that conspicuous red colour pattern elements are significantly associated with sympatric and parapatric populations in four genera. To our knowledge, this represents the first evidence of a Müllerian mimetic radiation in vipers. The putative mimetic patterns are rarely found in females. This appears paradoxical in light of the Müllerian prediction of monomorphism, but may be explained by divergent selection pressures on the sexes, which have different behaviours. We suggest that biased predation on active males causes selection for protective warning coloration, whereas crypsis is favoured in relatively sedentary females.