Insufficient Radiofrequency Ablation Promotes Hepatocellular Carcinoma Metastasis Through N6-Methyladenosine mRNA Methylation-Dependent Mechanism.

BACKGROUND AND AIMS: The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote HCC progression; however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains open for study. APPROACH AND RESULTS: Using an IRFA HCC orthotopic mouse model, we detected a higher level of m6 A reader YTH N6-methyladenosine RNA binding protein 1-3 (YTHDF1) in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model, and patients' HCC tissues. Functionally, gain-of-function/loss-of-function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases epidermal factor growth receptor (EGFR) m6 A modification in the vicinity of the 5' untranslated region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal-heat-induced up-regulation of EGFR level was further confirmed in the IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically. CONCLUSIONS: The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery combined with EGFR inhibitors to suppress HCC metastasis after RFA.

Direct exposure of the head to solar heat radiation impairs motor-cognitive performance.

Health and performance impairments provoked by thermal stress are societal challenges geographically spreading and intensifying with global warming. Yet, science may be underestimating the true impact, since no study has evaluated effects of sunlight exposure on human brain temperature and function. Accordingly, performance in cognitively dominated and combined motor-cognitive tasks and markers of rising brainstem temperature were evaluated during exposure to simulated sunlight (equal to ~1000 watt/m2). Acute exposure did not affect any performance measures, whereas prolonged exposure of the head and neck provoked an elevation of the core temperature by 1 °C and significant impairments of cognitively dominated and motor task performances. Importantly, impairments emerged at considerably lower hyperthermia levels compared to previous experiments and to the trials in the presents study without radiant heating of the head. These findings highlight the importance of including the effect of sunlight radiative heating of the head and neck in future scientific evaluations of environmental heat stress impacts and specific protection of the head to minimize detrimental effects.

42 °C heat stress pretreatment protects human melanocytes against 308-nm laser-induced DNA damage in vitro.

Vitiligo is a common depigment of skin disorder due to loss of functional melanocytes. Recently, the phototherapy with a 308-nm xenon-chloride excimer laser (UVB laser) is wildly used in vitiligo treatment. However, excessive UVB will induce photo-damage and photo-carcinogenesis in melanocytes. Previous studies revealed a protective effect of heat on UVB-induced melanocyte damage. In this study, we combined heat stress pretreatment with UVB to evaluate whether heat stress pretreatment has an ameliorative effect on UVB-induced damage. Human primary melanocytes (HMCs) were cultured and irradiated with a 308-nm laser with/without heat treatment. MTT assay, apoptosis analysis, and comet assay were conducted to monitor the damage of HMCs. Western blot and immunofluorescence staining were performed to assess the expression and subcellular localization of HSP70. HMCs heated at 42 °C for 1 h exhibit no cytotoxicity. Furthermore, preheat treatment attenuated the UVB laser-induced injury, reduced the DNA damage, and attenuated the cell apoptosis. The level and the localization of HSP70 determined the protective effects against UVB-induced DNA damage. Combining preheat treatment with a 308-nm xenon-chloride excimer laser would be a potential therapeutic method not only promotes the repigment of vitiligo but also reduces the UVB-induced photo-damage.

Initial Characterization of the Growth Stimulation and Heat-Shock-Induced Adaptive Response in Developing Lake Whitefish Embryos after Ionizing Radiation Exposure.

Ionizing radiation is known to effect development during early life stages. Lake whitefish (Coregonus clupeaformis) represent a unique model organism for examining such effects. The purpose of this study was to examine how ionizing radiation affects development in lake whitefish embryos and to investigate the presence of an adaptive response induced by heat shock. Acute exposure to 137Cs gamma rays was administered at five time points corresponding to major developmental stages, with doses ranging from 0.008 to 15.5 Gy. Chronic gamma-ray exposures were delivered throughout embryogenesis within a custom-built irradiator at dose rates between 0.06 and 4.4 mGy/day. Additionally, embryos were given a heat shock of 3, 6 or 9°C prior to a single acute exposure. Radiation effects were assessed based on survival, development rate, morphometric measurements and growth efficiency. Embryos showed high resistance to acute exposures with an LD50/hatch of 5.0 ± 0.7 Gy immediately after fertilization, increasing to 14.2 ± 0.1 Gy later in development. Chronic irradiation at all dose rates stimulated growth, with treated embryos up to 60% larger in body mass during development compared to unirradiated controls. Chronic irradiation also accelerated the time-to-hatch. A heat shock administered 6 h prior to irradiation reduced mortality by up to 25%. Overall, low-dose chronic irradiation caused growth stimulation in developing lake whitefish embryos and acute radiation mortality was reduced by a heat-shock-induced adaptive response.

Moderate Heat Stress Stimulates Repair of Photosystem II During Photoinhibition in Synechocystis sp. PCC 6803.

Examination of the effects of high temperature on the photoinhibition of photosystem II (PSII) in the cyanobacterium Synechocystis sp. PCC 6803 revealed that the extent of photoinhibition of PSII was lower at moderately high temperatures (35-42 °C) than at 30 °C. Photodamage to PSII, as determined in the presence of chloramphenicol, which blocks the repair of PSII, was accelerated at the moderately high temperatures but the effects of repair were greater than those of photodamage. The synthesis de novo of the D1 protein, which is essential for the repair of PSII, was enhanced at 38 °C. Electron transport and the synthesis of ATP were also enhanced at 38 °C, while levels of reactive oxygen species fell. Inhibition of the Calvin-Benson cycle with glycolaldehyde abolished the enhancement of repair of PSII at 38 °C, suggesting that an increase in the activity of the Calvin-Benson cycle might be required for the enhancement of repair at moderately high temperatures. The synthesis de novo of metabolic intermediates of the Calvin-Benson cycle, such as 3-phosphoglycerate, was also enhanced at 38 °C. We propose that moderate heat stress might enhance the repair of PSII by stimulating the synthesis of ATP and depressing the production of reactive oxygen species, via the stimulation of electron transport and suppression of the accumulation of excess electrons on the acceptor side of photosystem I, which might be driven by an increase in the activity of the Calvin-Benson cycle.

Targeting the heat shock response in combination with radiotherapy: Sensitizing cancer cells to irradiation-induced cell death and heating up their immunogenicity.

Radiotherapy represents an essential treatment option for the majority of cancer patients in different stages of their disease. Physical achievements of the recent years led to the implementation of high precision treatment planning procedures, and image-guided dose delivery is current state of the art. Yet, radiotherapy still faces several limitations with cancer intrinsic radioresistance being a key driver of therapeutic failure. Accordingly, the mechanisms orchestrating radioresistance and their therapeutic targeting by combined modality approaches are in the center of attention of numerous radiation oncologists. In the present review, we summarize and discuss therapeutic approaches that exploit the heat shock response, either by hyperthermia or by pharmacological heat shock protein inhibition, in combination with radiotherapy. These strategies appear particularly promising, since they sensitize cancer cells to irradiation-induced cell death and at the same time have proven the potential to promote systemic anti-tumor immune mechanisms, which may target not only locally surviving tumor cells, but also distant out-of-field metastases.

Small heat shock proteins can release light dependence of tobacco seed during germination.

Small heat shock proteins (sHSPs) function as ATP-independent molecular chaperones, and although the production and function of sHSPs have often been described under heat stress, the expression and function of sHSPs in fundamental developmental processes, such as pollen and seed development, have also been confirmed. Seed germination involves the breaking of dormancy and the resumption of embryo growth that accompany global changes in transcription, translation, and metabolism. In many plants, germination is triggered simply by imbibition of water; however, different seeds require different conditions in addition to water. For small-seeded plants, like Arabidopsis (Arabidopsis thaliana), lettuce (Lactuca sativa), tomato (Solanum lycopersicum), and tobacco (Nicotiana tabacum), light is an important regulator of seed germination. The facts that sHSPs accumulate during seed development, sHSPs interact with various client proteins, and seed germination accompanies synthesis and/or activation of diverse proteins led us to investigate the role of sHSPs in seed germination, especially in the context of light dependence. In this study, we have built transgenic tobacco plants that ectopically express sHSP, and the effect was germination of the seeds in the dark. Administering heat shock to the seeds also resulted in the alleviation of light dependence during seed germination. Subcellular localization of ectopically expressed sHSP was mainly observed in the cytoplasm, whereas heat shock-induced sHSPs were transported to the nucleus. We hypothesize that ectopically expressed sHSPs in the cytoplasm led the status of cytoplasmic proteins involved in seed germination to function during germination without additional stimulus and that heat shock can be another signal that induces seed germination.

Index of thermal stress for cows (ITSC) under high solar radiation in tropical environments.

This paper presents a new thermal stress index for dairy cows in inter-tropical regions, with special mention to the semi-arid ones. Holstein cows were measured for rectal temperature (T R), respiratory rate (F R) and rates of heat exchange by convection (C), radiation (R), skin surface evaporation (E S) and respiratory evaporation (E R) in the north eastern region of Brazil, after exposure to sun for several hours. Average environmental measurements during the observations were air temperature (T A) 32.4 °C (24.4-38.9°), wind speed (U) 1.8 m.s(-1) (0.01-11.0), relative humidity 63.6 % (36.8-81.5) and short-wave solar radiation 701.3 W m(-2) (116-1,295). The effective radiant heat load (ERHL) was 838.5 ± 4.9 W m(-2). Values for the atmospheric transmittance (τ) were also determined for tropical regions, in order to permit adequate estimates of the solar radiation. The average value was τ = 0.611 ± 0.004 for clear days with some small moving clouds, with a range of 0.32 to 0.91 in the day period from 1000 to 1300 hours. Observed τ values were higher (0.62-0.66) for locations near the seacoast and in those regions well-provided with green fields. Effects of month, location and time of the day were all statistically significant (P < 0.01). A total of 1,092 data were obtained for cows exposed for 1 to 8 h to sun during the day; in 7 months (February, March, April, July, August, September and November), 4 days per month on the average. A principal component analysis summarised the T R, F R, C, R, E S and E R measurements into just one synthetic variable (y 1); several indexes were then obtained by multiple regression of y 1 on the four environmental variables and its combinations, by using Origin 8.1 software (OriginLab Corp.). The chosen equation was the index of thermal stress for cows, ITSC = 77.1747 + 4.8327 T A - 34.8189 U + 1.111 U (2) + 118.6981 P V - 14.7956 P V (2) - 0.1059 ERHL with r (2) = 0.812. The correlations of ITSC with T R, F R, C, E S, R and E R were 0.275, 0.255, -0.493, -0.647, -0.818 and 0.075, respectively. Correlations of the index with the physiological variables are presented, and ITSC is compared to three other indexes.

Skin temperature during sunbathing--relevance for skin cancer.

It has been found that exposure to heat and infrared radiation (IR) can be carcinogenic, and that a combination of ultraviolet radiation (UVR) and IR possibly amplifies carcinogenesis. To investigate how the skin temperature is affected by sunbathing, we measured the skin temperature on 20 healthy volunteers over 6 days' sun holiday in Egypt. Temperatures were measured with an infrared thermometer gun at 8 skin sites on the volunteers while they were indoors in the morning and when sunbathing during the day. Skin temperatures were higher during sunbathing (33.5 °C ± 2.1 °C) (mean ± SD) than when indoors in the morning (32.6 °C ± 1.4 °C) (mean ± SD) (P < 0.0001). The average skin temperature for men was higher than for women by 0.40 °C in the morning (P = 0.02) and by 0.44 °C during sunbathing (P < 0.0001). Our results show that sunbathing has an impact on skin temperature, which possibly by activation of the heat shock response, is likely to contribute to the immediate and delayed effects of UV in a way that has to be found out in future studies.

Photothermic regulation of gene expression triggered by laser-induced carbon nanohorns.

The development of optical methods to control cellular functions is important for various biological applications. In particular, heat shock promoter-mediated gene expression systems by laser light are attractive targets for controlling cellular functions. However, previous approaches have considerable technical limitations related to their use of UV, short-wavelength visible (vis), and infrared (IR) laser light, which have poor penetration into biological tissue. Biological tissue is relatively transparent to light inside the diagnostic window at wavelengths of 650-1,100 nm. Here we present a unique optical biotechnological method using carbon nanohorn (CNH) that transforms energy from diagnostic window laser light to heat to control the expression of various genes. We report that with this method, laser irradiation within the diagnostic window resulted in effective heat generation and thus caused heat shock promoter-mediated gene expression. This study provides an important step forward in the development of light-manipulated gene expression technologies.

Loss of HSF1 results in defective radiation-induced G(2) arrest and DNA repair.

HSF1 is a transcription factor that plays a key role in the response to heat stress and was previously shown by us to also be essential for importation of p53 into the nucleus. Here we extend these studies and show that loss of HSF1 renders cells more sensitive to killing by ionizing radiation. Cells that lack a functional HSF1 were unable to arrest in G(2) after exposure to ionizing radiation, suggesting that HSF1 activity was essential for activation of this cell cycle checkpoint. In addition, cells with no HSF1 showed a reduced capacity to repair radiation-induced double-stranded DNA breaks. We found that in these cells 53BP1 did not accumulate at sites of DNA damage, suggesting that HSF1 was also essential for the functioning of this DNA damage mediator. Taken together our results indicate that HSF1 plays an important role in checkpoint activation and DNA repair and suggest that there is overlap between the heat stress response pathway and the pathway that responds to ionizing radiation.

Analysis of the bacterial heat shock response to photodynamic therapy-mediated oxidative stress.

Antimicrobial photodynamic therapy (PDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. We investigated whether PDT induced protective responses such as heat shock proteins (HSPs) in bacteria. Using the photosensitizer Toluidine Blue O (TBO) at sublethal PDT conditions, a seven-fold increase in bacterial HSP GroEL and a three-fold increase in HSP DnaK were observed in Escherichia coli post PDT. Pretreatment with 50°C heat for 30 min reduced PDT killing in both E. coli and in Enterococcus faecalis, with the most pronounced inhibition occurring at 50 µm TBO with 5 J cm(-2) 635 nm light, where E. coli killing was reduced by 2 log(10) and E. faecalis killing was reduced by 4 log(10). Finally, inhibition of the highly conserved chaperone DnaK using a small molecule benzylidene lactam HSP inhibitor potentiated (but not significantly) the effect of PDT at a TBO concentration of 2.5 µm in E. faecalis; however, this effect was not observed in E. coli presumably because inhibitor could not gain access due to Gram-negative permeability barrier. Induction of HSPs may be a mechanism whereby bacteria could become resistant to PDT and warrants the need for further study in the application of dual PDT-HSP-inhibition therapies.

Immunohistochemical evaluation of the heat shock response to nonablative fractional resurfacing.

Despite the emergence of nonablative fractional resurfacing (NFR) as a new therapeutic modality for skin photoaging, little is known about the molecular events that underlie the heat shock response to different treatment parameters. Human subjects are treated with a scanned 1550-nm fractional laser at pulse energies spanning 6 to 40 mJ and a 140-µm spot size. The heat shock response is assessed immunohistochemically immediately through 7 days posttreatment. At the immediately posttreatment time point, we observe subepidermal clefting in most sections. The basal epidermis and dermal zones of sparing are both found to express HSP47, but not HSP72. By day 1, expression of HSP72 is detected throughout the epidermis, while that of HSP47 remains restricted to the basal layer. Both proteins are detected surrounding the dermal portion of the microscopic treatment zone (MTZ). This pattern of expression persists through day 7 post-NFR, although neither protein is found within the MTZ. Immediately posttreatment, the mean collagen denaturation zone width is 50 µm at 6 mJ, increasing to 202 µm at 40 mJ. The zone of cell death exceeds the denaturation zone by 19 to 55% over this pulse energy range. The two zones converge by day 7 posttreatment.

Cambios en el perfil de ácidos grasos y microestructura de aguacate hass tratado con microondas / Fatty acids profile and microstructure of avocado puree after microwave heating

El objetivo del presente trabajo fue evaluar los cambios en el perfil de ácidos grasos y microestructura en el puré de aguacate por efecto del tratamiento térmico con microondas. Los resultados obtenidos muestran que el componente mayoritario del perfil de ácidos grasos fue el ácido oleico, seguido del ácido palmítico, linoleico y palmitoleico. El perfil de ácidos grasos de los purés no presentó cambios al ser calentado con microondas (p < 0.05). Así mismo, no se detectaron ácidos grasos trans. Por otra parte, cambios significativos en la microestructura del puré de aguacate tratado con microondas fueron detectados. Se encontró que a tiempos menores de 40 s, se conserva en mayor grado la estructura de los idioblastos del aguacate, mientras que a tiempos mayores de 40 s, se observaron zonas de rompimiento de las paredes y membranas celulares, liberando el aceite y mostrando restos de idioblastos vacíos, lo cual se correlaciona con la evaluación sensorial en donde se encontró que a tiempos de calentamiento de 60 s, las muestras fueron calificadas como aceitosas o grasas.

Changes in the fatty acid profile and the microstructure of avocado puree after microwave treatment were evaluated. The main components of the fatty acid profile were oleic, palmitic, linoleic and palmitoleic acids. Fatty acids profile of microwaved avocado puree did not show significant changes (p < 0.05). Trans fatty acids were not detected. Microwaved avocado puree showed significant changes in its microstructure. Samples treated with microwaves for less than 40 s preserved the cells shape, causing only a minimal modification. On the other hand, microwave treated avocado puree using more than 40 s, showed a disruption of idioblast oil cells, releasing the oil contained on them. The results might be explained based on the sensory evaluation that was performed on the microwaved avocado puree, where samples at 60 s showed oily texture and grassy flavor.

Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

Gene expression analysis of a human lymphoblastoma cell line exposed in vitro to an intermittent 1.9 GHz pulse-modulated radiofrequency field.

This study was designed to determine whether radiofrequency (RF) fields of the type used for wireless communications could elicit a cellular stress response. As general indicators of a cellular stress response, we monitored changes in proto-oncogene and heat-shock protein expression. Exponentially growing human lymphoblastoma cells (TK6) were exposed to 1.9 GHz pulse-modulated RF fields at average specific absorption rates (SARs) of 1 and 10 W/kg. Perturbations in the expression levels of the proto-oncogenes FOS, JUN and MYC after exposure to sham and RF fields were assessed by real-time RT-PCR. In addition, the transcript levels of the cellular stress proteins HSP27 and inducible HSP70 were also monitored. We demonstrated that transcript levels of these genes in RF-field-exposed cells showed no significant difference in relation to the sham treatment group. However, concurrent positive (heat-shock) control samples displayed a significant elevation in the expression of HSP27, HSP70, FOS and JUN. Conversely, the levels of MYC mRNA were found to decline in the positive (heat-shock) control. In conclusion, our study found no evidence that the 1.9 GHz RF-field exposure caused a general stress response in TK6 cells under our experimental conditions.

Attenuation of chronic thermotolerance by KNK437, a benzylidene lactam compound, enhances thermal radiosensitization in mild temperature hyperthermia combined with low dose-rate irradiation.

PURPOSE: We investigated whether the attenuation of chronic thermotolerance by KNK437, a heat shock protein inhibitor, can modify the effect of thermal radiosensitization in mild temperature hyperthermia (MTH) combined with low dose-rate irradiation (LDRI). MATERIALS AND METHODS: The human lung adenocarcinoma cell line A549 was simultaneously exposed to LDRI with MTH at 41 degrees C and KNK437 at a dose of 100 microM. Cell survival was estimated by a clonogenic assay. Cell cycle change during treatment was analyzed by flow cytometry. Expression levels of the heat shock proteins hsp72, hsp27 and heat shock factor 1 (HSF-1) were measured by Western blotting. RESULTS: KNK437 inhibited the expression of inducible hsp72 and hsp27, but produced no change in the mobility shift of HSF-1. The cytotoxicity of LDRI was enhanced by MTH. The survival curve for LDRI + MTH revealed no development of chronic thermotolerance up to 48 h. Simultaneous LDRI and KNK437 treatment also resulted in enhanced cell killing. The radiosensitizing effect of KNK437 was enhanced by simultaneous exposure of the cells to MTH. Flow cytometry analysis of cell cycle progression demonstrated marked G2 arrest and mild G1 arrest with LDRI alone, but mild G1 arrest with MTH alone, and mild G2-M, S-phase accumulation with KNK437 alone. The marked G2 arrest caused by LDRI was partially suppressed by the addition of MTH, and was also suppressed by KNK437 treatment. CONCLUSIONS: Exposure of A549 cells to KNK437 caused inhibition of hsp72 and hsp27 expression. The addition of KNK437 increased not only thermosensitivity to MTH, but also radiosensitivity to LDRI. KNK437 also enhanced the MTH-induced radiosensitization under these experimental conditions.

915 MHz microwaves and 50 Hz magnetic field affect chromatin conformation and 53BP1 foci in human lymphocytes from hypersensitive and healthy persons.

We used exposure to microwaves from a global system for mobile communication (GSM) mobile phone (915 MHz, specific absorption rate (SAR) 37 mW/kg) and power frequency magnetic field (50 Hz, 15 muT peak value) to investigate the response of lymphocytes from healthy subjects and from persons reporting hypersensitivity to electromagnetic field (EMF). The hypersensitive and healthy donors were matched by gender and age and the data were analyzed blind to treatment condition. The changes in chromatin conformation were measured with the method of anomalous viscosity time dependencies (AVTD). 53BP1 protein, which has been shown to colocalize in foci with DNA double strand breaks (DSBs), was analyzed by immunostaining in situ. Exposure at room temperature to either 915 MHz or 50 Hz resulted in significant condensation of chromatin, shown as AVTD changes, which was similar to the effect of heat shock at 41 degrees C. No significant differences in responses between normal and hypersensitive subjects were detected. Neither 915 MHz nor 50 Hz exposure induced 53BP1 foci. On the contrary, a distinct decrease in background level of 53BP1 signaling was observed upon these exposures as well as after heat shock treatments. This decrease correlated with the AVTD data and may indicate decrease in accessibility of 53BP1 to antibodies because of stress-induced chromatin condensation. Apoptosis was determined by morphological changes and by apoptotic fragmentation of DNA as analyzed by pulsed-field gel electrophoresis (PFGE). No apoptosis was induced by exposure to 50 Hz and 915 MHz microwaves. In conclusion, 50 Hz magnetic field and 915 MHz microwaves under specified conditions of exposure induced comparable responses in lymphocytes from healthy and hypersensitive donors that were similar but not identical to stress response induced by heat shock.

Heat shock induces phosphorylation of histone H2AX in mammalian cells.

Heat shock induces a variety of biological events including gene activation, cell cycle arrest, and apoptosis. Heat shock has recently been shown to be potentially useful when combined with radiation in cancer therapy, probably because, in mammalian cells, heat inhibits the repair of double-strand breaks (DSBs) induced by ionizing radiation. It remains unclear, however, whether heat shock by itself induces DSBs. In this communication, we present the first evidence that heat shock induces the phosphorylated form of histone H2AX, which is thought to be generated at the chromatin proximal to DSB sites. These results suggest that heat shock induces DSBs in mammalian cells and may provide direct evidence to explain previous reports on DSB-related events occurring after heat shock treatment.