Quantitative evaluation of abscopal effect based on biological effective dose in breast cancer tumors in mice

Background: Due to abscopal effect, cell damage may occur outside of the radiation field and the quantification of this effect is one of the most challenging debates in radiation therapy. The aim of this study was to estimate the abscopal effect induced in non-irradiated tumors quantitatively by means of biological effective dose [BED]

Materials and Methods: Breast tumors using 4T1 and MC4-L2 cells, were induced into the flank region of Balb/c mice. When palpable, the tumor on one side of the body was irradiated with dose of 28Gy in 14 fractions and 2 Gy per fraction, 5 fractions per week. The tumor on the other side of the body was shielded with a lead plate. BED was estimated based on tumor volume. H and E staining and TUNEL assay were performed to assess histological changes and apoptosis in irradiated and non-irradiated tumors

Results: The effect of radiation on non-irradiated tumors was more than that on irradiated ones. The BED was 4.49 and 6.74 in 4T1 and MC4-L2 tumors, respectively. The ratio of the tumor volume in the last fraction to that in the first fraction for irradiated 4T1 tumors was 2.32 and in non-irradiated was 1.50. This ratio in irradiated and non- irradiated MC4-L2 tumors was 2.64 and 1.98, respectively. The number of apoptotic cells was higher in non-irradiated tissues

Conclusion: Results indicate that the occurrence of abscopal effect is highly depends on the type of tumor. By means of the abscopal effect, more radiation dose can be delivered to the tumor and metastatic sites

Induction of DNA damage, apoptosis and micronuclei in peripheral blood lymphocytes following injection of contrast media in patients with abdominal CT scan

Background: Medical diagnostic procedures such as X-ray and computed Tomography [CT] scan account for considerable percent of patient's exposure to ionizing radiation. The exposure of cells to Ionization radiation results in induction of DNA damage and chromosomal aberrations. Contrast media [CM] are widely used in diagnostic radiology and CT scan. The aim of this study was to study adverse genetic effects of combined administration of non ionic contrast media and low dose X-rays in peripheral blood Lymphocytes of patients following abdominal CT scan

Materials and Methods: A total of 55 patients underwent abdominal CT scan with injection of non ionic contrast media [30 patients with omnipaque 300 mg/ml and 25 patients with visipaque 270 mg/ml] as well as 13 patients undergoing abdominal CT scan [without contrast], selected as control group, were enrolled in this study. Peripheral blood leukocytes were obtained in heparin containing tubes and cultured for the micronucleus test, or were directly used for apoptosis and DNA damage with the neutral comet assay

Results: The frequency of micronuclei, apoptosis and percentage of DNA damage was increased in most patients after the injection of contrast media, significantly different from the control group as compared with the samples obtained before and after injection of contrast media [P<0.05]

Conclusion: The present study suggest that non ionic contrast media [omnipaque 300 mg/ml and visipaque 270 mg/ml] may cause a significant increase of cytogenetic damage in peripheral blood lymphocytes. This effect might be caused by the enhancement of radiation dose by CM that eventually may lead to the manifestation of ill health such as cancer

Inherent radio sensitivity and its impact on breast cancer chemo-radiotherapy

About 10% of apparently normal individuals are sensitive to clastogenic effects of physico-chemical agents. More than 45% of breast cancer patients' exhibit elevated radiosensitivity. Although the nature of inherent radiosensitivity is not fully understood, but insufficiency and impaired DNA repair mechanism might be prime cause of radiosensitivity. This is evident from genetically affected individuals such as ataxia telangiectasia, severe combined immunodeficiency, Xeroderma pigmentasum, Fanconi anemia who show sensitivity to ionizing radiation, ultraviolet light and alkylating agents. All these genetic diseases are caused due to impaired DNA damage repair mechanism. Radiation therapy [RT] is a common and effective way of treatment in several types of malignant tumors. Some cancer patients suffer from side effects of RT such as radiation induced early or late adverse responses in normal tissues within weeks, months, or even years post irradiation, due to intrinsic radiosensitivity. The RT efficiency limitation raises from ionizing radiation toxicity reactions in normal tissues. An appropriate protocol to prevent or treat these side effects, has not been developed yet. Molecular pathways involved in adverse responses to cancer treatment agents have not been well defined. Identification of molecular mechanisms may be promising to enhance the output of treatment technologies and overall survival of cancer patients. Several techniques such as microarray technology has been used to clarify molecular mechanisms involved in radiosensitivity by finding genes related to RT normal tissue responses. DNA repair, apoptosis, cell cycle, and growth factor associated genes are the most important candidates in this field?

Potent radioprotective effect of herbal immunomodulator drug [IMOD] on mouse bone marrow erythrocytes as assayed with the micronucleus test

Background: Although numerous natural or synthetic drugs have been tested for their radioprotective capacity, yet no suitable drug has been introduced for routine clinical use. In this study the radioprotective effect of "a new herbal immunomodulator" commercially known as IMOD, specifically made to decrease the side effects of HIV virus, was investigated on mouse bone marrow cells. Materials and Methods: Female NMRI mice [in a group of five] were exposed to 2 Gy gamma radiation following three days of intravenously injection [IV] of IMOD at various doses. Mice were sacrificed 48 and 72 h after irradiation. Bone marrow was flushed and slides for bone marrow smears were prepared according to standard method. After staining slides in May Grunwald and Giemsa, polychromatic erythrocytes [PCE] and normochromatic erythrocytes [NCE] were scored for presence of micronucleus [MN]. Results: The results showed that gamma irradiation increased the frequency of micronuclei dramatically and excreted cytotoxic effect of cell proliferation. Injection of various doses of IMOD before irradiation however, led to a considerable reduction in the frequency of micronuclei in bone marrow erythrocytes as well as cellular toxicity. Conclusion: Results indicated radioprotective capability of IMOD with a dose reduction factor [DRF] of about 2.3 at a dose of 20 mg/kg body weight. The considerably high DRF might be indicative that IMOD besides being an immunomodulator might also posses' antioxidant property

Increased Mercury release due to exposure to electromagnetic radiation as a limiting factor for using dental amalgam

Background: although it is one of the most toxic nonradioactive elements, mercury is widely used in dental amalgam. Mercury is a toxic element which can damage various organs such as central nervous system, renal, respiratory and hematologic systems. The adverse health impacts associated to exposure to some common sources of electromagnetic fields including laptop computers, mobile phones, MRI and mobile phone jammers have been evaluated by our laboratory in our previous investigations. In this study, we aimed to evaluate the effect of X ray exposure on microleakage of amalgam restoration

Materials and Methods: standardized class V cavities were prepared on the buccal surfaces of 46 non-carious freshly extracted human premolars. The teeth were randomly divided into experimental and control groups. Experimental group were exposed to X-ray using an intraoral radiography machine at 60 kVp, 0.1 s, 7 mA with 2.5 mm Al total filtration. The absorbed dose was 245.0 +/- 0.5 microGy. All specimens were placed in 2 % basic fuchsin solution for 24 hours. Then the specimens were sectioned and microleakage was assessed according to dye penetration using a stereomicroscope. Statistical analysis was performed with the Mann-Whitney U-test

Results: microleakage was significantly higher in the X-ray exposed teeth compared to those of the non-irradiated samples

Conclusion: the results of the present study suggest that X-ray exposure increased microleakage of amalgam restorations

effect of delivering compensating doses on the survival of F10B16 melanoma and 4T1 breast adenocarcinoma treated with prolonged radiation delivery time

Increasing the complexity in modern radiotherapy techniques have increased the delivery time lowering consequently the treatment efficacy. Through simulating the delivery time delay encountered in such techniques, its' effect on two cancer cell lines and the compensating doses given to prevent such effect was investigated. F10B16 and 4T1 cancer cell lines were exposed to simulated clinical fractionated radiotherapy procedures commonly used in complex techniques. The survival rate of the cells exposed to 2, 4, and 6 Gy of ionizing radiation with two equal subfractions given at various time intervals between the fractions [0.25-4 hours] were determined using the MTT assay. Then, relevant compensating doses were calculated and their efficacy in counterbalancing the time delay was assessed. The cells' survival was increased with prolonged treatment times in the fractionated groups being more significant at the lower time intervals [up to 2 hours] and for the higher radiosensitive cells [4T1]. Giving the compensated doses decreased the survival of the cells. Delivering appropriate compensating doses to the prolonged fractionated groups can counterbalance the effect of time delays encountered in complex radiotherapy techniques

Future role of vitamin C in radiation mitigation and its possible applications in manned deep space missions: survival study and the measurement of cell viability

Astronauts will be exposed to both chronic space radiation and acute high doses of energetic radiation of solar particle events in long-term deep space missions. The application of radioprotectors in space missions has basic limitations such as their very short time window as well as their acute toxicity and considerable side effects. The aim of the present study was to investigate the potential radiation mitigation effect of vitamin C that is known as an effective antioxidant and free radical scavenger. One hundred twenty male Wistar albino rats weighing 250-300 g were randomized into the following study groups: I, control; II, Only exposure to gamma-radiation [LD50/30]; treated with a single dose of vitamin C, III, 1h before irradiation, IV, V and VI, 1h, 12h and 24 h after irradiation. Measurement of cell viability and proliferation was also performed by using MTT cell proliferation assay. The survival rate in animals received vitamin C 1h, 12h and 24h after irradiation were 55%, 60%, and 80%, respectively. The viability of cells in animals received vitamin C 1h, 12h and 24h after irradiation were 94.9%, 99.0%, and 100%, respectively. The viability of the cells in animals only exposed to gamma rays was 50.1%. These findings reveal that a single dose of vitamin C can potentially be used up to 24 hours after exposure to reduce the detrimental effects of high levels of ionizing radiation in cases such as the occurrence of currently unpredictable solar particle events

gamma-H2AX as a protein biomarker for radiation exposure response in ductal carcinoma breast tumors: experimental evidence and literature review

H2AX is a histone variant that is systematically found and ubiquitously distributed throughout the genome. DNA double-strand breaks [DSBs] induce phosphorylation of H2AX at serine 139 [gammaH2AX], an immunocytochemical assay with antibodies recognizing gammaH2AX has become the gold standard for the detection of DSBs. The importance of this assay to investigate different individual responses to gamma irradiation was reviewed and an example of different radiation responses of ductal carcinoma tumors with different expression levels of ATM and HER-2 was discussed. The ductal carcinoma breast tissues were exposed to 4 Gy gamma rays and after 24 hours incubation in modified RPMI 1640 medium in 37°C with CO2, the frequency of residual induced DSB was assessed using gammaH2AX assay compared to pair normal adjacent and control breast tissues. Results showed that the frequency of DSB dramatically increased in both tumor and normal irradiated tissues, compared to sham non-irradiated controls. Tumors with HER-2 over expression showed significantly lower residual DSB frequencies after 24 hours post irradiation incubation time, whereas this frequency dramatically increased in ATM under expressed tissues. Our data showed that different tissues may have different radio-sensitivity and ATM under- and HER-2 over-expression may lead to higher and lower sensitivity to ionizing radiation, respectively. This may be due to the role of ATM in DSB repair and HER-2 in EGFR downstream signaling pathway that with the use of cell survival mechanisms ends to resistance against radiation effects and activation of PI3K/ACT that leads to DSB repair

Natural ventilation considerations for radon prone areas of Ramsar

In Iran, architectures are often unaware of the risk of radon inhalation and how to reduce radon levels. Furthermore, radon considerations are not implemented in construction methods, construction materials and building utilization by regulatory authorities. In this study after reviewing the meteorological changes of Ramsar over the past 50 years [1955-2005], a novel design for constructing dwellings in radon prone areas is introduced. Out of building interventions such as planting wind-tunnel-making trees will be discussed in another paper. Ramsar soil samples with 4 levels of specific activities [extremely hot, severely hot, very hot, and hot] were placed in a model house. Radon level monitoring was performed by using a PRASSI portable radon gas survey meter. For extremely hot soil samples, the radon levels inside the model house when windows were closed for 24 hours were 1615 +/- 516 Bq/m3. When windows which were in the wind direction or opposite the wind direction were opened for 24 h, the radon level decreased to 89 +/- 286 and 139 +/- 314 Bq/m3, respectively. Interestingly, when crossed windows were opened for the same duration, Radon level was 144 +/- 92 Bq/m3. In cold seasons, when windows are usually closed, Chimney effect reduced the radon level to 323 +/- 641. For severely hot, very hot and hot soil samples, natural ventilation-based interventions effectively reduced the radon level. Results obtained in this study clearly show that natural ventilation-based simple cost-effective interventions can significantly reduce the radon concentration in radon prone areas of Ramsar

Alterations of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers in human blood serum due to long term exposure to high levels of natural background radiation in Ramsar, Iran

Ramsar [Mazandran province] is known for its extremely high levels of natural background radiation. Although no excess cancer rate is reported in these areas by epidemiological studies, the study of tumor markers in the inhabitants of these areas may shed some light on the impact of high levels of background radiation on cancer induction. The level of background gamma radiation as well as indoor radon was determined using RDS-110 and CR-39 dosimeters. Thirty five individuals from a high background radiation area [HBRA] and 53 individuals from a normal background radiation area [NBRA] were randomly selected to participate in the study. Commercial ELISA kits [sandwich type ELISA tests] were used to measure the serum levels of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers. Among the eight biomarkers investigated, the means of PSA, CA15.3, CA125, CA19.9 and AFP concentrations between the HBRAs and NBRAs were not significantly different. However, Cyfra21, CEA and Tag72 in HBRA group revealed statistically significant increases compared to those of NBRA group [P<0.05]. Furthermore, a statistically significant correlation between the external gamma dose as well as indoor radon level and the concentration of CEA [P<0.001], Cyfra-21[P<0.001] and TAG 72 [P<0.001 and 0.01 respectively] biomarkers were observed. Chronic exposure to high background radiation induces significant alterations in Cyfra21, CEA and Tag72 levels. We believe that studies with other relevant tumor markers might overcome the limitations of epidemiological studies on cancer incidence in high background radiation areas

Radiosensitizing effects of gemcitabine on aerobic and chronically hypoxic HeLa and MRC5 cells in-vitro

Gemcitabine [2', 2'-difluoro-2'- deoxycytidine, an analogue of deoxycytidine] is a relatively new drug with wide range of anti-cancer activity. In this study, radiosensitizing effects of gemcitabine was investigated on HeLa and MRC5 human originated cell lines under both chronically hypoxic and normoxic conditions using the micronucleus [MN] assay. For induction of chronic hypoxia, the cell culture flasks were saturated with N2 gas. To evaluate the radiosensitizing effects, in the presence of the non-genotoxic concentration [1ng/ml] of gemcitabine, cells were exposed to different doses [0.5, 1, 2 Gy] of X-ray in both chronically hypoxic and normoxic conditions. Results showed that there was no significant difference in MN induction under chronically hypoxic and normoxic condition when using 1 ng/ml gemcitabine alone, however in the absence of drug, MN induction was significantly different in irradiated cells [P<0.01]. Radiosensitizing effects of gemcitabine in chronic hypoxic condition was greater than normoxic condition in both cell lines [P<0.01], although more pronounced in HeLa cells. Radiosensitizing effects and greater dose modifying factor of gemcitabine under depleted oxygen condition is not clearly understood. It might be due to depletion of deoxynocleotides pools via inhibition of ribonucleotide reductase and mismatched nucleosides incorporation into DNA after radiation exposure

Is it time to shed some light on the black box of health policies regarding the inhabitants of the high background radiation areas of Ramsar?

Although there are substantial experimental, epidemiological and clinical evidences that high doses of ionizing radiation cause cancer and other detrimental biological effects, the health effects of human exposure to chronic low dose radiation exposures are still poorly known. People in some areas around the world live in dwellings with radiation and radon levels as much as more than 200 times the global average. Inhabited areas with high levels of natural radiation are found in different areas around the world including Yangjiang, China; Kerala, India; Guarapari, Brazil and Ramsar, Iran. Ramsar in northern Iran is among the world's well-known areas with highest levels of natural radiation. Annual exposure levels in areas with elevated levels of natural radiation in Ramsar are up to 260 mGy y[-1] and average exposure rates are about 10 mGy y[-1] for a population of about 2000 residents. Due to the local geology, which includes high levels of radium in rocks, soils, and groundwater, Ramsar residents are also exposed to high levels of alpha activity in the form of ingested radium and radium decay progeny as well as very high radon levels in their dwellings. Based on the findings obtained by studies on the health effect of high levels of natural radiation in Ramsar, as well as other high background radiation areas, no consistent detrimental effect has been detected so far. Further research is needed to clarify if the regulatory authorities should set limiting regulations to protect the inhabitants against such extraordinary elevated levels of natural radiation

Short-term exposure to high levels of natural external gamma radiation does not induce survival adaptive response

In some areas of Ramsar, a city in northern Iran, residents receive a much higher annual radiation exposure than is permitted for radiation workers. Induction of adaptive response in residents of Ramsar has been reported previously. In this study induction of such a response in short term exposure to high background levels of gamma radiation is investigated. Fifty male NMRI mice were randomly divided into four groups of 10-17 animals and 53 Wistar rats were randomly divided into five groups of 10-12 animals were studied. Animals in the 1[st] group were kept for 7 days in an outdoor area with normal background radiation while the 2[nd], 3[rd], 4[th] and 5[th] [in case of rats] groups were kept in 3 different outdoor areas with naturally elevated levels of gamma radiation. Animals were then exposed to a lethal dose of 8 Gy gamma radiation. For mice, 30 days after exposure to lethal dose, the survival fraction for the control group was 40% while the 2[nd], 3[rd], and 4[th] groups had survival rates of 20%, 33.30%, and 35.20%, respectively. For rats, 30 days after exposure to the lethal dose, the survival fraction for the control group was 40% while the 2[nd], 3[rd], 4[th] and 5[th] groups had survival rates of 20%, 41.6%, 60.0% and 35.7%, respectively. Results indicate that short term exposure to extremely high levels of natural gamma radiation [up to 196 times higher than the normal background] do not lead to induction of survival adaptive response

G2 chromosomal radiosensitivity and background frequency of sister chromatid exchanges of peripheral blood lymphocytes of breast cancer patients

Chromosomal alterations play an important role in carcinogenesis. Enhanced chromosomal radiosensitivity is shown for many cancer predisposition conditions including breast cancer. In this study chromosomal radiosensitivity and the frequency of background sister chromnatid exchanges [SCE] in lymphocytes of normal individuals and breast cancer patients was compared. G2 assay was performed on peripheral blood lymphocytes obtained from 60 breast cancer patients and 50 normal control. Blood culture was initiated and cells were irradiated with 1 Gy gammarays 4 h prior to harvesting. After metaphase preparations and slide making, chromatid aberrations were scored. For SCE studies, blood samples from 30 breast cancer patients and 30 normal control were studied. 24 hours after culture initiation, 5-bromodeoxy uridine [BrdU] was added and cells were harvested 48 hours after addition of BrdU. Slides were stained in Hoechst 33258 and exposed to UVA source, then stained in Giemsa. Results indicated that the frequency of radiation induced chromatid breaks was significantly higher in breast cancer patients compared to normal control [p<0.01]. From radiosensitivity point of view, 12% of normal control and 47% of breast cancer patients showed elevated chromatid radiosensitivity. Frequency of background SCE was significantly higher in lymphocytes of breast cancer patients compared to lymphocytes of control [p<0.05]. Elevated chromosomal radiosensitivity and higher frequency of SCE in lymphocytes of breast cancer patients might be indicative of genomic instability of these cells. Increased radiosensitivity could also be due to defects in DNA repair genes involved in breast cancer formation

Protective effects of famotidine and vitamin C against radiation induced cellular damage in mouse spermatogenesis process

Radioprotective effect of famotidine was previously shown on radiation induced micronuclei and chromosomal aberrations in human peripheral lymphocytes and mouse bone marrow cells; however, its radioprotective property has never been studied in mouse spermatogenesis. It was also shown that vitamin C as an antioxidant also exert its radioprotective effect on many biological systems, but in some studies no protective effect is reported. Mice were injected by small and nontoxic amount of vitamin C and famotidine [3 and 2 micro g] inter-testicular 2 hours before irradiating by gamma ray. 29 days after irradiation, mice were sacrificed and testes were removed, weighed and either fixed for histological study or homogenized in 1.5 mL de-ionized water and 0.5 mL SDS solution. Sperm head count was done under a light microscope. Survival fractions were calculated and plotted as a function of dose of gamma rays. The sperm head count in groups treated with vitamin C and famotidine before gamma irradiation show significant increase compared to groups only irradiated by gamma rays [p<0.01]. Values of calculated dose reduction factor [DRF] are 2 and 2.68 for vitamin C and famotidine respectively. Both vitamin C and famotidine could reduce radiation induced pathological alterations in seminiferous tubules. These results suggest that vitamin C and famotidine have radioprotective property and could reduce cytotoxic effect of radiation in mouse spermatogenesis, one of the most radiosensitive biological systems. The possible mechanism of protection by famotidine and vitamin C might be radical scavenging. The radioprotection index for famotidine was found to be more than vitamin C

Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields [ELF-EMF] have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to ELF-EMF may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields [3, 50 and 60 Hz, sinusoidal, 3h, and 4 mT]. Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous ELF-EMF [50 Hz, sinusoidal, 3 h, 4 mT]. Metaphase plates were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of ELF-EMF on primary or established cell lines. Results indicate that by increasing the frequency of ELF-EMF, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Results obtained indicate that ELF-EMF has the potential for induction of chromosomal aberrations in all cell types

Construction of a dose- response curve by induction of premature chromosome condensation for biological dosimetry

Premature Chromosome Condensation [PCC] appears to have a possible utility for biological dosimetry purposes. The PCC technique may be adapted for cases of suspicion of overexposure where sampling is performed at least one day after an accident. For this purpose, human blood samples were exposed in vitro to [60] Co up to 10 Gy and the PCC technique was performed immediately after irradiation. Analysis of excess PCC fragments distribution showed an over dispersion and the dose-effect relationship was best characterized by linear regression

Modification of 10 cGy neutron or gamma-rays induced chromosomal damages by hyperthermia: an in vitro study

To evaluate the effects of hyperthermia [HT] on the frequency of chromosomal aberrations induced by a low dose of neutron or gamma-rays in human peripheral blood lymphocytes. Blood samples were exposed to HT [41.5°C for 30 and 60min, 43°C for 15 and 30min], 10 cGy neutron or gamma-rays, HT + neutron/gamma, and neutron/gamma + HT. After standard cell culture, harvesting, fixation and staining, the chromosomal damages were scored in metaphase plates. HT alone at 41.5°C did not induce chromatid or chromosome aberrations, however, the frequency of damages was significantly higher at 43°C [P<0.05]. Furthermore, the chromosomal damages was significantly different when cells were irradiated with neutron or gamma-rays alone [P<0.01]. HT 1 hr post neutron/gamma irradiation significantly induced higher chromosome damages in comparison to HT 1 hr before irradiation [P<0.05]. The chromosomal damages were remarkably higher when cells were irradiated with neutron then heated at 43°C for 30 min. Since increasing frequency of chromosome damages increases probability of cell death, application of HT after neutron irradiation [instead of X-or gamma-rays] might be considered as a procedure for cells killing in radiotherapy

Free hydroxyl radical dosimetry by using 1 MHz low level ultrasound waves

In order to quantify effects of ultrasound irradiation parameters under therapeutic condition, especially sonodynamic therapy, it is initially necessary to evaluate inertial cavitation activity in vitro conditions; therefore, in this study, the effect of 1 MHz low level ultrasound based on OH radicals generated by acoustic inertial cavitation in aqueous solution was monitored by their reaction with terephthalic acid [TA] to produce fluorescent 2-Hydroxyterephthalate acid [HTA] by spectrofluorometry method [Terephtalic acid dosimetry]. The study was designed to measure hydroxyl radicals in a field near to 1 MHz sonotherapy probe in progressive mode and low level intensity. The effect of ultrasound irradiation parameters [1MHz] containing duty factor, mode, intensity ultrasound and, time sonication in hydroxyl radical production have been considered. After preparation of solution of dosimetry and plotting calibration curve of spectrofluorescence, the effect of mode of sonication [continuous and pulsating], duty factor [20-80%], intensity [0-2 W/cm[2], with step of 0.5 W/cm[2]], and sonication time [0-60min with step time of 10min] without increasing temperature to more than 3°C to determine the effective exposure in low level ultrasound were evaluated. The fluorescence intensity of TA solution before and after irradiation, in all cases was measured, and the results were reported as Mean +/- Standard Deviation [SD]. The result of experiments related to sonication mode for 1MHz ultrasound irradiation [2 W/cm[2]] show that continuous mode of sonication is 29% higher fluorescence intensity than the pulse mode in 80% duty cycle for sonodynamic therapy. With compensation of irradiation time for 1MHz sonication in different duty cycles, fluorescence intensity in continuous mode is 22% higher than the pulse mode in average. The amount of hydroxyl radicals production versus ultrasound intensity, and sonication time show with increasing intensity or sonication time in continuous mode, the hydroxyl radical production is linearity increased [R=0.99]. The results show that the terephthalic acid dosimetry is suitable for detecting and quantifying free hydroxyl radical as a criterion of inertial cavitation production over a range of condition in medical ultrasound fields