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

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

Evaluation of changes of kidney parmeter in New Zealand rabbits subseqent to 90 days exposure to uranyl nitrate in drinking water

This study was undertaken to examine the reversibility of renal injury in the male New Zealand white rabbits subsequent to a 90-days exposure to uranyl nitrate [UN] in drinking water. Animals were exposed for 90 days to uranyl nitrate in their drinking water [24 or 500mg/l]. Control group were given municipal tap water. The indicators of kidney function measured in this study included glucose [marker of tubular] microalbumin[marker of glomerular] and marker for cell toxicity was alkaline phosphatase. Urinary glucose was found to be significantly different and positively correlated with uranium intake for rabbits. Microalbuminuria was found to be significantly different but this different is in normal range. Increase of alkaline phosphatase at weeks 2, 4, 6 was correlated with uranium intake, but at weeks 8, 10, 13 excretion of alkaline phosphatase was decreased. These results suggest that chronic ingestion of uranium in drinking water affect kidney function and to the proximal tubule, rather than glomerul

[Evaluation of kidney function in Male New zealand white rabbits, subsequent to a 90 days exposure to uranyl nitrate in the drinking water]

This study was undertaken to examine the reversibility of renal injury in the male New Zealand white rabbits, subsequent to a 90-days exposure to uranyl nitrate [UN] in the drinking water. Animals were exposed for 90 days to uranyl nitrate in their drinking water [24 or 500mg/l] The control group were given municipal tap water. The biomarkers of kidney function measured in this study included beta-2 micro globulin [marker of tubular], micro albumin [marker of glomerular] and the marker for cell toxicity was catalase. Excretion of beta-2 micro globulin was to be significantly different and was correlated with uranium intake for rabbits in early weeks. Microalbuminuria was found to be significantly different but this different was within normal range. Catalasuria was not significantly different in this study. These results suggest that chronic ingestion of uranium in the drinking water affects kidney function and is related to the proximal tubule, rather than glomerul

Determination of dose-response relationship in cultured human lymphocytes for biological dosimetry

Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosimetry of overexposed individuals. In this study, the frequency of unstable chromosome aberration in blood lymphocytes was used to estimate radiation dose received by individuals. Evaluation of dose using a calibration curve produced elsewhere may have a significant uncertainty; therefore, experiments were performed to produce a dose-response curve using an established protocol of international atomic energy agency

Materials and Methods: Lymphocytes in whole peripheral blood obtained from healthy individuals, were exposed to various doses of gamma radiation [0.25 - 4 Gy]. Then after 1 hour of incubation in 37°C, were cultured in complete RPMI-1640 medium. 500 mitoses were analysed for the presence or absence of unstable chromosomal aberrations for each radiation dose after the standard metaphase preparation and staining slides

Results and Conclusion: Intercellular distribution of dicentric chromosomes at each radiation dose has been used to contrast a dose-response curve. It seems that dose-effect relationship follows with the linear-quadratic model. There is a good agreement between our dose-response curves with similar published studies by other laboratories