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Radiobiological Evaluation and Optimisation of Treatment Plans
Published in W. P. M. Mayles, A. E. Nahum, J.-C. Rosenwald, Handbook of Radiotherapy Physics, 2021
This University of Michigan study was extended to a total of 203 patients (Dawson et al. 2002), but analysed with the LKB model. The patients had either unresectable intrahepatic cancer or metastatic spread to the liver from colorectal carcinoma. All patients were treated twice a day on dose-escalation protocols. Sixty-one patients were treated with whole-liver irradiation, with 20 of them receiving a subsequent boost to a partial liver volume, and the remaining 142 were treated with partial liver irradiation. Either fluorodeoxyuridine or bromodeoxyuridine was used as a radiation sensitiser for the first 4 weeks. For the whole group, the LKB parameter values for grade ≥3 RILD were TD50 = 43.3 Gy (41.9 Gy – 52.8 Gy), m = 0.18 (0.14 – 0.24) and n = 1.1 (0.88 – 1.6). These are consistent with the relatively narrow range of values in Table 44.4 for patients with Child-Pugh A or better liver function and no hepatitis B virus infection (QUANTEC, Pan et al. 2010), but very different from the Burman et al. (1991) parameters. The large value of n would suggest that the mean liver dose would be a good predictor of damage but they also found a threshold volume effect.
Multiple Sclerosis
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
A significant new finding, reported this year by Gipps and Kidson,49 is that MS patients exhibit higher sensitivity to ionizing radiation than age» and sex-matched controls. This finding agrees with earlier reports that MS cells show an increased rate of sister chromatid exchange after exposure to low doses of 5-bromodeoxyuridine.50 The sensitivity appears to be a general property of the cells of an individual. Family studies suggest autosomal dominant inheritance, with low penetrance, but the abnormality has not been mapped to a specific chromosomal locus. The values obtained (for frequency of γ-induced chromosome aberrations in PHA-stimulated lymphocytes) approach those obtained with the same technique in patients homozygous for ataxia-telangiectasia. In the latter disease, radiosensitivity is associated with a DNA-processing defect, resulting in reduced capacity to cope with DNA damage, and affects the development and function of both neural and immune systems.
Methods to Study the Vasculature in ADPKD
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Patricia Outeda, Terry Watnick
5-Bromo-2′-deoxyuridine (bromodeoxyuridine [BrdU]) is a thymidine analogue that is incorporated into the DNA of dividing cells during S phase of the cell cycle and can be easily detected by standard immunohistochemical techniques using a primary antibody directed against BrdU.136,137 BrdU incorporation is therefore an indicator of DNA synthesis and is used as a marker of cell proliferation.
Genotoxicity of nedaplatin in cultured lymphocytes: modulation by vitamin E
Published in Drug and Chemical Toxicology, 2023
Muntaha S. Al-Khdour, Omar F. Khabour, Laith N. Al-Eitan, Karem H. Alzoubi
Cell cultures were prepared by inoculating 1 mL of whole blood to 9 mL of PB-MAX medium in 50 mL culture flasks. For SCEs experiments, cultures were treated with 5-bromodeoxyuridine at 20 µg/mL final concentration (Al-Eitan et al.2020). Culture flasks were kept at 37 °C/5% CO2 for 72 hours. Four experimental groups were used: control, nedaplatin (1 µg/mL), Vit E (10 µg/mL), and nedaplatin + VE. The used nedaplatin concentration is within the range that has been shown to induce genotoxicity to cultured human cells (El-Shafie et al.2020). Nedaplatin was freshly prepared before use and was dissolved in culture media to obtain a stock solution of 1 mg/mL. Vitamin E was dissolved in ethanol as previously described and was added during culture establishment (Alqudah et al.2018). Cultures were treated with nedaplatin in the last 24 hours of incubation time. Control cultures and nedaplatin alone group were treated also with an equivalent amount of vehicle to that used in Vit E groups. We did not include positive control in the experiments as the genotoxicity of platinum anticancer agents is well documented (Brabec and Kasparkova 2005).
Anticlastogenic, antimutagenic, and cytoprotective properties of Orthosiphon stamineus ethanolic leaves extract
Published in Drug and Chemical Toxicology, 2022
Dhamraa W. Al-Dulaimi, Aman Shah Abdul Majid, Hussein M. Baharetha, Mohamed B. Khadeer Ahamed, Sarah Furqan Faisal, Raghdaa Hamdan Al Zarzour, Chern Ein Oon, Amin Malik Shah Abdul Majid, Loiy E. Ahmed Hassan
According to the recommendations of OECD guideline 473 (Guideline, 1997) for investigation, the potential of chemical compounds and plant extract to induce CA. Human peripheral blood samples were obtained from four healthy nonsmokers donors (age: 20–24). The cultures were established by adding 0.5 ml of heparinized blood to (5 ml) RPM1 supplemented with 15% fetal bovine serum, 4 Mm L-glutamine, 100 IU/mL penicillin, 100 ug/mL streptomycin, and 10 ug/ml phytohaemagglutinin (PHA). The cultures incubated at 37 °C, after 24 h incubation, MMC was added at 0.5 µg/ml. For SCE, the test was performed according to Unal et al. (2013) 10 μg/ml Bromodeoxyuridine (Bdur) was added at the beginning of cultures and incubated in the dark for 72 h. The culture media treated with three different concentrations (200, 100, and 50 ug/ml) of Et.O.s leave extract added simultaneously and 1 h before and after (pre and post–treatment, respectively) MMC. Positive and negative controls were treated with MMC and PBS, respectively, without plant extract. The cultures incubated for further 48 h (total incubation period about 72 h at 37 °C. Demecolicin (0.05 ug/ml) was added to the cultures 1 h prior harvesting (Saraiva et al.2009).
Sodium arsenite-induced detriment of cell function in Leydig and Sertoli cells: the potential relation of oxidative damage and antioxidant defense system
Published in Drug and Chemical Toxicology, 2020
Banu Orta Yilmaz, Nebahat Yildizbayrak, Melike Erkan
Cell proliferation was determined by using a colorimetric immunoassay kit (Roche Molecular Biochemicals, Mannheim, Germany) based on the measurement of bromodeoxyuridine (BrdU) incorporation during DNA synthesis. After experimental incubation (24, 48, and 72 h), the proliferating cells were marked by BrdU at 24 h. The labeling media was then removed, and the cells were fixed for 30 min with 200 µL FixDenat solution for denaturated genomic DNA. After removing FixDenat samples were incubated for 90 min with anti-BrdU POD at room temperature. At the end of incubation, the cells were washed three times with 200 μL washing solution before added 100 μL substrate. Optical density was measured at 450 nm wavelength in the spectrophotometer to determine DNA synthesis and therefore proliferation. The proliferation of the control cells, which were not treated with the test substance, was assumed to be 100%, and the proliferation of experimental cells were expressed in percentages.