Exposure to chronic noise and fractionated X-ray radiation elicits biochemical changes and disrupts body weight gain in rat

The aim was to assess the developmental and biochemical effects resulting from separate and combined exposures to radiation and noise in adult male Sprague-Dawley rats. For 21 days, animals were exposed daily (1) to whole-body 121 kVp X-ray exposure (cumulative dose=5 Gy), (2) to random intermittent noise band-limited between 0.4 and 20 kHz; 2 h day(-1) 86 decibels (dB) and (3) to combined exposures. Control animals were housed under ambient noise conditions 55 dB A-weighted (dBA) and sham-exposed to X-rays. Body weight gain was significantly reduced in animals exposed to either X-rays or noise, and the loss was more pronounced in animals exposed to both conditions. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone was altered by the treatment conditions. This study corroborated previous reports that ionizing radiation exposure increased plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHDG), but no effect was observed in animals co-exposed to chronic noise. Plasma big-endothelin-1 (Big ET-1) was significantly reduced in animals exposed to a combination of noise and X-rays. The results indicated that (1) adaptation to chronic noise appeared to occur at the level of the hypothalamic pituitary adrenal (HPA) response, in spite of a compromise in overall body weight gain; and (2) ionizing radiation exposure might alter systems activated by stressor exposure and/or act independently to influence health outcomes.     

Increased body weight in C57BL/6 female mice after exposure to ionizing radiation or 60Hz magnetic fields

PURPOSE: The purpose of this investigation was to determine whether early treatment with ionizing radiation and/or chronic magnetic field (MF) exposure affected body weight in female mice. MATERIALS AND METHODS: Weanling C57BL/6 female mice were irradiated with four equal weekly cobalt-60 exposures (total cumulative doses: 3.0, 4.0, 5.1Gy) and/or received chronic lifetime exposure to 1.4 mT 60 Hz circularly polarized MF or ambient MF. The body weights of 2280 mice were recorded at 35 age intervals, and analysis of variance was used to compare the mean differences from baseline weights between treatment groups and sham-exposed controls. RESULTS: A highly statistically significant effect of ionizing radiation on body weight was observed at 28 age intervals (p < or = 0.001), and for MF exposure at 10 age intervals (p < or = 0.001). During the young adult growth phase, mice exposed only to MF exhibited < or =0.5 g greater weight gain relative to sham-exposed controls (p = 0.0001). The effect of ionizing radiation alone was inversely related to dose, with the largest weight increases observed in all of the irradiated groups after 9-12 months (p = 0.0001). CONCLUSIONS: Treatment with split-dose ionizing radiation at an early age and chronic exposure to a residential power frequency MF were found to produce small but significant increases in body weight.     

Increased body weight in C57BL/6 female mice after exposure to ionizing radiation or 60Hz magnetic fields

Purpose: The purpose of this investigation was to determine whether early treatment with ionizing radiation and/or chronic magnetic field (MF) exposure affected body weight in female mice. Materials and methods: Weanling C57BL/6 female mice were irradiated with four equal weekly cobalt-60 exposures (total cumulative doses: 3.0, 4.0, 5.1Gy) and/or received chronic lifetime exposure to 1.4mT 60 Hz circularly polarized MF or ambient MF. The body weights of 2280 mice were recorded at 35 age intervals, and analysis of variance was used to compare the mean differences from baseline weights between treatment groups and sham-exposed controls. Results: A highly statistically significant effect of ionizing radiation on body weight was observed at 28 age intervals (p h 0.001), and for MF exposure at 10 age intervals (p h 0.001). During the young adult growth phase, mice exposed only to MF exhibited h 0.5g greater weight gain relative to sham-exposed controls (p = 0.0001). The effect of ionizing radiation alone was inversely related to dose, with the largest weight increases observed in all of the irradiated groups after 9-12 months (p = 0.0001). Conclusions: Treatment with split-dose ionizing radiation at an early age and chronic exposure to a residential power frequency MF were found to produce small but significant increases in body weight.     

Differential response of two cell lines sequentially irradiated with low X-ray doses

An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90?–?95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.     

Chronic low dose exposure of hospital workers to ionizing radiation leads to increased micronuclei frequency and reduced antioxidants in their peripheral blood lymphocytes

Abstract

Purpose: The regular low dose occupational exposure to ionizing radiation may induce deleterious health effects, which may be of particular interest to medical radiation workers who daily handle X-ray machines. Human peripheral blood lymphocytes are able to retain the signature of radiation-induced DNA damage, therefore, the present study was undertaken to investigate the DNA damage and antioxidants status in hospital workers occupationally exposed to low doses of X-rays.

Materials and methods: The peripheral blood lymphocytes of the occupationally exposed and control groups matched for age, gender, tobacco usage, and alcohol consumption were cultured and micronuclei frequency was determined. Activities of antioxidant enzymes and lipid peroxidation were also estimated in their plasma.

Results: The micronuclei frequency in the occupationally exposed group (n?=?33), increased significantly (p?<?.0001) followed by reduced glutathione-s-transferase (p?<?.01) and catalase (p?<?.001) activities, and increased lipid peroxidation (p?<?.05) when compared to the control group (n?=?33). Occupational exposure resulted in an effective dose ranging between 3.14 to 144.5 mSv (40.88?±?39.86mSv) depending on the employment duration of 3–29 years (10.33?±?7.05 years). A correlation between the micronuclei frequency (p?<?.05) and catalase activity (p?<?.05) existed in the occupationally exposed individuals depending on the smoking habit, age, duration of employment, cumulative exposure dose and number of patients handled per day.

Conclusions: We have observed that protracted low dose exposure to ionizing radiation is an inevitable occupational hazard leading to persistence of oxidative stress and increased genomic instability in the radiological technicians depending on the time spent with X-rays, cumulative dose received and the number of patients handled daily raising the risk of cancer development.     

Fractionated exposure to low doses of ionizing radiation results in accumulation of DNA damage in mouse spleen tissue and activation of apoptosis in a p53/Atm-independent manner

Purpose: While the effects of high doses of ionizing radiation (IR) are relatively well characterized, the molecular mechanisms underlying cellular responses to prolonged exposure to low doses of radiation remain largely under-investigated.

Materials and methods: Here, we addressed the DNA damage and apoptotic response in the spleen tissue of C57BL/6 male mice after fractionated exposure to X-rays within the 0.1–0.5?Gy dose range.

Results: The response to initial exposure to 0.1?Gy of IR was characterized by increased DNA damage and elevated levels of apoptosis. Subsequent exposures (cumulative doses of 0.2 and 0.3?Gy) resulted in adaptive response-like changes, represented as increased proliferation and apoptotic response. Cumulative doses of 0.4 and 0.5?Gy were characterized by accumulation of DNA damage and reactivation of apoptosis and apoptosis-related proteins. Additionally, spleen cells with irreversible damage caused by radiation can undergo apoptosis via activation of p38, which does not necessarily involve the Atm/p53 pathway.

Conclusions: Fractionated exposure to low doses of X-rays resulted in accumulation of DNA damage in the murine spleen and induction of apoptotic response in p53/Atm-independent manner. Further studies are needed to understand the outcomes and molecular mechanisms underlying cellular responses and early induction of p38 in response to prolonged exposure to IR.     

Changes in activity and structure of lysosomes from liver of mouse irradiated in vivo

Purpose: Lysosomes may have an important role in response to ionizing radiation. Moreover, radiation could affect autophagy, which process involves the activity of lysosomal enzymes. In the present study, the effect of ionizing radiation on the lysosomal compartment of mouse liver was investigated after in vivo exposure.

Materials and methods: Morphology and ultrastructure of hepatocytes were assessed by light and electron microscopy, and activities of selected lysosomal enzymes were assessed in 12, 36 and 120?h after exposure to the mean dose of 1?Gy. The levels of autophagy-related proteins LC3-II and p62 were compared by Western blotting between untreated and irradiated animals (120?h after exposure).

Results: Increased number of autophagic vacuoles in hepatocytes from exposed animals was documented in the ultrastructural study; destroyed mitochondria were the dominant component of such vacuoles. Moreover, an increased activity of lysosomal hydrolases was observed after exposure. However, levels of autophagy substrates LC3-II and p62 were barely affected in exposed animals 120?h after irradiation when the accumulation of autophagic vacuoles was observed.

Conclusion: Effects of irradiation included an increased number of autophagic vacuoles, especially of autophagosomes, and increased activity of lysosomal enzymes. However, putative markers of autophagic flux were not observed, which suggested suppression of the completion of the radiation-mediated autophagy pathway.     

Prenatal irradiation and spatial memory in mice: investigation of critical period.

Pregnant CD1 mice were exposed on various gestational or postnatal days to 1 Gy of 250 kV X-rays. Ten adult, male offspring from each exposure condition were tested in a radial arm maze. Compared to sham-exposed control mice, acquisition of spatial information was unimpaired in animals exposed on gestational days 13 or 15, or on postnatal day 10, but animals exposed on gestational day 18 or postnatal day 1 showed sustained deficits in acquisition. These results appear consistent with the known time-course for the proliferation and migration of the dentate granule cells of the hippocampus in the mouse, and are discussed in relation to the dependence on hippocampal integrity of the acquisition and use of spatial information. The results suggest that comparable deficits in mental function might be expected in humans similarly exposed to ionizing radiation during periods of proliferation and migration of the dentate granule cells.     

Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation

PURPOSE: In order to identify supportive evidence of radiation exposure to cells, we analyzed the relationship between exposure to ionizing radiation and the induction of deletions in mitochondrial DNA (mtDNA). MATERIALS AND METHODS: Using human hepatoblastoma cell line, HepG2 and its derivatives, HepG2-A, -89 and -400, established after long term exposure to X-ray, mtDNA deletions were analyzed by polymerase chain reaction (PCR) and real-time PCR after cells were subjected to radiation and genotoxic treatments. RESULTS: Common Deletion (CD), the most extensively studied deletion of mtDNA, was induced within 24 h after exposure to 5 Gray (Gy) of X-rays and was associated with replication of mtDNA. CD became undetectable several days after the exposure due to the death of cells containing mitochondria within which CD had been induced. Furthermore, we found a novel mtDNA deletion that consisted of a 4934 base-pair deletion (4934del) between nucleotide position 8435 and 13,368. A lower dose of ionizing radiation was required to induce the 4934del than for CD and this was independent of the quality of radiation used and was not induced by treatments with hydrogen peroxide (H(2)O(2)) and other genotoxic reagents including bleomycin. CONCLUSION: CD is induced by ionizing radiation, however, the amount of CD detected at a certain point in time after radiation exposure is dependent on the initial frequency of CD induced and the death rate of cells with mtDNA containing CD. The novel mtDNA deletion found in this study, therefore, will be used to determine whether cells were exposed to ionizing radiation.     

Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation

Purpose: In order to identify supportive evidence of radiation exposure to cells, we analyzed the relationship between exposure to ionizing radiation and the induction of deletions in mitochondrial DNA (mtDNA).

Materials and methods: Using human hepatoblastoma cell line, HepG2 and its derivatives, HepG2-A, -89 and -400, established after long term exposure to X-ray, mtDNA deletions were analyzed by polymerase chain reaction (PCR) and real-time PCR after cells were subjected to radiation and genotoxic treatments.

Results: Common Deletion (CD), the most extensively studied deletion of mtDNA, was induced within 24 h after exposure to 5 Gray (Gy) of X-rays and was associated with replication of mtDNA. CD became undetectable several days after the exposure due to the death of cells containing mitochondria within which CD had been induced. Furthermore, we found a novel mtDNA deletion that consisted of a 4934 base-pair deletion (4934del) between nucleotide position 8435 and 13,368. A lower dose of ionizing radiation was required to induce the 4934del than for CD and this was independent of the quality of radiation used and was not induced by treatments with hydrogen peroxide (H₂O₂) and other genotoxic reagents including bleomycin.

Conclusion: CD is induced by ionizing radiation, however, the amount of CD detected at a certain point in time after radiation exposure is dependent on the initial frequency of CD induced and the death rate of cells with mtDNA containing CD. The novel mtDNA deletion found in this study, therefore, will be used to determine whether cells were exposed to ionizing radiation.     

Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

IntroductionNuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN).MethodsThe present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period.ResultsIn nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05).ConclusionsThis study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.     

The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.     

声预处理对强噪声引起听力损伤保护作用的研究(英文)

目的 探讨低频声预处理对强噪声及中频强噪声引起听力损伤的保护作用。方法 两组声预处理组豚鼠在中心频率０．５ｋＨｚ８５ｄＢ倍频带噪声作用下,连续暴露４ｄ（６ｈ／ｄ）后,在无噪声情况下恢复３ｄ。随后分别在中心频率０．５ｋＨｚ和１ｋＨｚ１１０ｄＢ的倍频带噪声下,暴露１ｈ。两组对照组豚鼠不经声预处理,分别直接暴露在中心频率０．５ＫＨｚ和１ｋＨｚ１１０ｄＢ的倍频带噪声下,暴露１ｈ。两组对照组豚鼠不经声预处理     

Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice

Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation.

Materials and methods: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0.1) or intermediate/high (0.2–1?Gy) doses of radiation either by acute X-rays exposure or protracted exposure to low dose-rate γ-radiation was used to analyse by PCR the presence of illegitimate TR gene rearrangements.

Results: Radiation exposure does not increase the onset of TR gene trans-rearrangements in irradiated mice. In mice where it happens, trans-rearrangements remain sporadic events in developing T lymphocytes.

Conclusion: We concluded that low dose/low dose rate ionizing radiation (IR) exposure does not lead to widespread inactivation of ATM-dependent mechanisms, and therefore that the mechanisms enforcing genetic stability are not impaired by IR in developing lymphocytes and lymphocyte progenitors, including BM-derived hematopoietic stem cells, in low dose/low dose rate exposed mice.     

Differential response of two cell lines sequentially irradiated with low X-ray doses

An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90 - 95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.     

Gold nanoparticles as dose-enhancement agent for kilovoltage X-ray therapy of melanoma

Purpose: Melanoma is mainly treated by surgery and rarely with radiation because of the high radioresistance of this tumor. Nevertheless, radiotherapy is the preferred treatment modality for unresectable lesions and avoiding cosmetic disfigurement caused by surgical excision. This study investigated the therapeutic advantage of gold nanoparticles (AuNPs) for kilovoltage X-ray treatment of melanoma.

Materials and methods: Commercial AuNPs were evaluated for cytotoxicity and cellular internalization. The sensitivity of human skin melanoma cells to 150 and 450 kVp X-ray exposure was assessed in terms of clonogenicity with or without spherical AuNP treatment.

Results: AuNP treatment elicited dose enhancement effect on melanoma cells exposed to kilovoltage X-rays. Treatment with 320?μM 50?nm AuNPs before exposure to 150 kVp X-rays at 2?Gy resulted in clonogenic cell death equivalent to that caused by 4.3?Gy X-rays without AuNP treatment.

Conclusion: AuNPs of 50?nm in size can regulate melanoma cells in kilovoltage X-ray treatment by functioning as dose-enhancement agent and thus improving radioresponse of the cells. Melanomas of stages T1–T3 gain therapeutic benefits from 150 kVp X-ray treatment.     

The magnitude and time-dependence of the apoptotic response of normal and malignant cells subjected to ionizing radiation versus hyperthermia

Purpose:?The purpose of the study was to examine the optimal time of exposure and dose of heat and ionizing radiation that results in the killing of human cancer cells in vitro via apoptosis vs. necrosis.

Materials and methods:?Human mammary carcinoma, colorectal carcinoma and normal bovine capillary endothelial (BCE) cell lines were subjected to 20 Gy ionizing radiation and 6, 12, 24, and 72 h later assessed for apoptosis using detection of apoptotic bodies and caspase assays. Necrosis was detected by loss of cells from the surface and lactate dehydrogenase (LDH) release. The colorectal carcinoma cells were subjected to hyperthermia using temperatures ranging from 39 – 44°C for 5, 15 or 45 min. exposures and at varying times post-treatment, apoptosis and necrosis were measured.

Results:?In response to ionizing radiation, none of the cells underwent necrosis and some cell types apoptosed 24 and 72 h posttreatment. The colorectal cancer cells exhibited a steady increase of apoptosis at 6, 12, and 24 h. When these cells were exposed to 40°C for 5 min, caspases increased within 6 h and a significant fraction (50%) of cells apoptosed. If the time of exposure to 40°C was increased to 15 or 45 min, 80% and 100% of the dying cells apoptosed, respectively. A temperature of 39°C did not cause cell death even after 45 min exposures. If heat was elevated to 42 or 44°C, increased necrosis was observed with a corresponding decrease in apoptosis.

Conclusions:?These studies reveal time and temperature dependent in vitro cell responses to ionizing radiation and water-bath hyperthermia.     

A phenomenological model for the dynamics of cell cycle in responding to X-rays

Objective To establish a model to predict the cell-cycle process in response to ionizing radiation.Methods Human choroidal malignant melanoma 92-1 cells were used and the cell cycle distribution of cel...     

Effects of Low Dose Rate (0·003–0·025 Gy/h) Chronic X-irradiation on Radioresistant and Radiosensitive L5178Y Mouse Lymphoma Cells

Summary

Cultures of radioresistant (LY-R) and radiosensitive (LY-S) strains of L5178Y mouse lymphoma cells were exposed continuously to X-rays delivered at dose rates ranging from 0·003 to 0·025 Gy/h for up to 35 days. Populations of both strains proliferated actively during the exposure, but the growth rates were reduced in a dose rate-dependent manner. The reduction of growth rate occurred for strain LY-S earlier during the exposure and at lower dose rates than for strain LY-R. The survival (as measured by colony forming ability) of strain LY-R was affected only slightly at all dose rates applied. For strain LY-S, a decrease in the surviving fraction was observed in the initial part of the exposure. This decrease was followed by a plateau and eventually by an increase, in some cases to values close to the control level. The increase in the surviving fraction indicated that the radioresistance of the exposed LY-S cells had increased. This pattern was particularly clear for dose rates greater than 0·014 Gy/h. The pre-irradiated cells exhibited radioresistance when exposed to acute X-radiation after termination of the chronic exposure. The increase in radiation resistance was stable for at least 70 days after termination of the protracted exposure. These results show that mutagenic and/or selective phenomena leading to an increase in radiation resistance of mammalian cells can be caused by protracted exposures to X-rays at dose rates permitting active proliferation.     

Cellular effects of high-intensity focused continuous wave ultrasound alone and in combination with X-rays

Purpose : To investigate the cellular effects of 1.1 MHz high-intensity focused continuous wave (CW) ultrasound alone and in combination with X-rays. Materials and methods : V79 cells were exposed to ultrasound of different intensities for 30 s (non-hyperthermic conditions). In the combined treatments, cells were exposed to ultrasound (63 W/cm 2) either before or after 2 Gy X-irradiation. Cellular effects studied were clonogenic survival, DNA strand breaks (pulsed-field gel electrophoresis, DNA precipitation assay) and membrane integrity (morphological analysis). Results : With increasing ultrasound intensity, cell survival decreased in a dose-dependent manner as the induction of DNA strand breaks, the fraction of cells with lost membrane integrity and cell lysis increased. In the treatments with combined exposures, the regimen with X-rays before ultrasound had a nearly additive effect on cell kill, whereas the reverse regimen with ultrasound exposure before X-irradiation resulted in a synergistic effect (p < 0.012). Conclusions : High-intensity focused CW ultrasound induces an intensity-dependent reduction in clonogenic survival in V79 cells, which seems to depend on both DNA and membrane damage. Combined exposures of ultrasound and X-rays resulted in a synergistic reduction in cell survival when cells were exposed to ultrasound before X-rays but not for the reverse regimen. Thus, a larger fraction of the repairable sublethal cell damage induced by an initial ultrasound exposure was rendered non-repairable by a subsequent X-ray exposure than if the reverse treatment order was used.