scholarly journals The relationship between absorbed dose and DNA Damage in Lymphocytes after radionuclide therapy

2016 ◽  
Vol 118 ◽  
pp. S37-S38
Author(s):  
U. Eberlein ◽  
H. Scherthan ◽  
C. Bluemel ◽  
M. Peper ◽  
C. Lapa ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radionuclide Therapy ◽  
Absorbed Dose ◽  
The Relationship

scholarly journals Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC

2021 ◽  
Author(s):  
Heribert Hänscheid ◽  
Philipp E. Hartrampf ◽  
Andreas Schirbel ◽  
Andreas K. Buck ◽  
Constantin Lapa
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Agent ◽  
Somatostatin Receptor ◽  
Absorbed Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogue ◽  
Target Tissue ◽  
Peptide Receptor ◽  
Intraindividual Comparison ◽  
Administered Activity

Abstract Purpose The radiolabelled somatostatin analogue [177Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [177Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Results In comparison to [177Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [177Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [177Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [177Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.

scholarly journals α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

2021 ◽  
Author(s):  
S. Schumann ◽  
U. Eberlein ◽  
C. Lapa ◽  
J. Müller ◽  
S. Serfling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Absorbed Dose ◽  
Peripheral Blood Mononuclear ◽  
Absorbed Doses ◽  
Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

scholarly journals A multibiomarker approach in rats to assess the impact of pollution on Sinos River, Southern Brazil

2010 ◽  
Vol 70 (4 suppl) ◽  
pp. 1223-1230 ◽  
Author(s):  
C. Rechenmacher ◽  
AM. Siebel ◽  
A. Goldoni ◽  
CR. Klauck ◽  
T. Sartori ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Water Quality ◽  
Dna Damage ◽  
Quality Analysis ◽  
Microbiological Analysis ◽  
Southern Brazil ◽  
Anthropogenic Contamination ◽  
Water Analyses ◽  
The Impact ◽  
The Relationship

The aim of this study was to determine the feasibility of combining water quality analysis with different biomarkers to characterise the relationship between anthropogenic contamination and biotic response in the Sinos River, southern Brazil. Wistar rats were studied using three biomarkers combined with physical, chemical and microbiological analysis to assess the effects of pollution at four sampling sites. The induction of oxidative stress was quantified by MDA levels in peripheral blood, lymphocyte DNA damage was determined using the comet assay, and histopathological changes were analysed in the liver. After sampling, animals were allowed to drink the river water during a 48 hours period. No increase in oxidative stress and DNA damage was observed. However, liver damage was observed in the animals exposed to water samples, indicating that the Sinos River is contaminated with hepatotoxic substances. Water analyses confirmed that water quality decreased downriver.

Cytogenetic Damage of Human Lymphocytes in Humanized Mice Exposed to Neutrons and X Rays 24 h After Exposure

2021 ◽  
Vol 161 (6-7) ◽  
pp. 352-361
Author(s):  
Qi Wang ◽  
Younghyun Lee ◽  
Monica Pujol-Canadell ◽  
Jay R. Perrier ◽  
Lubomir Smilenov ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Exposure ◽  
Human Lymphocytes ◽  
Absorbed Dose ◽  
Chromosome 1 ◽  
X Rays ◽  
Chromosomal Dna ◽  
Humanized Mouse Model ◽  
Significant Difference

Detonation of an improvised nuclear device highlights the need to understand the risk of mixed radiation exposure as prompt radiation exposure could produce significant neutron and gamma exposures. Although the neutron component may be a relatively small percentage of the total absorbed dose, the large relative biological effectiveness (RBE) can induce larger biological DNA damage and cell killing. The objective of this study was to use a hematopoietically humanized mouse model to measure chromosomal DNA damage in human lymphocytes 24 h after in vivo exposure to neutrons (0.3 Gy) and X rays (1 Gy). The human dicentric and cytokinesis-block micronucleus assays were performed to measure chromosomal aberrations in human lymphocytes in vivo from the blood and spleen, respectively. The mBAND assay based on fluorescent in situ hybridization labeling was used to detect neutron-induced chromosome 1 inversions in the blood lymphocytes of the neutron-irradiated mice. Cytogenetics endpoints, dicentrics and micronuclei showed that there was no significant difference in yields between the 2 irradiation types at the doses tested, indicating that neutron-induced chromosomal DNA damage in vivo was more biologically effective (RBE ∼3.3) compared to X rays. The mBAND assay, which is considered a specific biomarker of high-LET neutron exposure, confirmed the presence of clustered DNA damage in the neutron-irradiated mice but not in the X-irradiated mice, 24 h after exposure.

scholarly journals Comet Test in Saliva Leukocytes of Pre-School Children Exposed to Air Pollution in North Italy: The Respira Study

2020 ◽  
Vol 17 (9) ◽  
pp. 3276 ◽  
Author(s):  
Claudia Zani ◽  
Elisabetta Ceretti ◽  
Ilaria Zerbini ◽  
Gaia Claudia Viviana Viola ◽  
Francesco Donato ◽  
...  
Keyword(s):  
Air Pollution ◽  
Dna Damage ◽  
School Children ◽  
Urban Areas ◽  
Outdoor Exposure ◽  
Airborne Pollutants ◽  
Exposure Variable ◽  
Two Measures ◽  
The Relationship ◽  
Indoor And Outdoor

Air pollution is a well-known problem for human health, especially for children living in highly polluted urban areas. This study aimed to assess the relationship between airborne pollutants concentration and biomarkers of DNA damage in the buccal mucosa cells of pre-school children. DNA damage was investigated with comet test in saliva leukocytes taken from sputum of 3- to 6-year-old children living in Brescia, Northern Italy, collected during two consecutive winter seasons (2012–2013). The daily levels of PM10, PM2.5, NO2, CO, SO2, benzene and O3 in urban air were collected for the whole period. A questionnaire filled in by the children’s parents was used to evaluate indoor and outdoor exposure. DNA damage in saliva leukocytes was evaluated in 152 children and the means of tail intensity and visual score as DNA damage were 6.2 ± 4.3 and 182.1 ± 30.9, respectively. No demographic and indoor or outdoor exposure variable was associated with the two measures of DNA damage. No significant association between air pollution and DNA damage in children’s buccal leukocytes was found. In this study, the comet assay does not appear to be a valuable biomarker to detect DNA damage in children exposed to high levels of air pollutants, such as PM10, PM2.5 and NO2.

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