Evaluation of the reticulocyte micronucleus assay in patients treated with radioiodine for thyroid cancer

Grawé, Jan; Biko, Johannes; Lorenz, R.; Reiners, Christoph; Stopper, Helga; Vershenya, Stanislav; Vukićević, Vladimir; Hempel, Klaus

doi:10.1016/j.mrgentox.2005.01.010

Cited by 39 publications

(25 citation statements)

References 27 publications

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“…The rarity of Retics CD71+ , coupled with the low rate of micronucleus formation, makes high analysis rates an essential characteristic. These data, coupled with recent reports (27)(28)(29), suggest that Retics CD71+ may represent a viable alternative to lymphocyte-based analyses. Retics offer several advantages, including a low blood volume requirement, no need for cell culture, and compatibility with an automated scoring methodology.…”

Section: Discussionsupporting

confidence: 58%

“…Since the spleen of most other species eliminate micronucleated erythrocytes from circulation, the use of rat, canine, non-human primate, and human blood was considered counterintuitive. Indeed, although splenic filtration does dilute the effect observed in blood relative to the bone marrow compartment, much data have been reported establishing that circulating Retics may represent a suitable target population for studying genotoxicant-induced micronuclei, even for species with efficient splenic activity (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). It has been reported that assay sensitivity can be realized for blood-based analyses by restricting interrogation to the most immature fraction of Retics (16,19,(21)(22)25), and also by increasing the number of Retics evaluated (30).…”

Section: Introductionmentioning

confidence: 99%

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Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Dertinger¹,

Miller²,

Brewer³

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

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This study evaluated the utility of human blood micronucleated reticulocyte (MN CD71+ ) frequency measurement as a cytogenetic damage biomarker. The analytical methodology was flow cytometry in conjunction with a previously described three color fluorescence labeling technique that includes anti-CD71 to focus analyses on the most immature fraction of reticulocytes [Dertinger et al., Environ. Molec. Mutagen., 44:427-435 (2004)]. Blood specimens from fifty self-reported healthy adult volunteers were studied. In addition to MN CD71+ measurements, blood plasma folate and B 12 levels were assessed, since these variables tend to influence other indices of cytogenetic damage. Timecourse data are also provided for ten cancer patients undergoing treatment. For these subjects, frequency of MN CD71+ was measured immediately before therapy, and daily during the first week of chemotherapy and/or fractionated radiotherapy. For the group of healthy volunteers, the variables of age, and folate and B 12 levels demonstrated no significant effect on MN CD71+ frequency. In addition, no difference was observed between pre-treatment MN CD71+ values for cancer patients compared with healthy volunteers. Regarding chemotherapy and/or partial body radiotherapy, elevated frequencies were observed upon initiation of treatment for 9 of the 10 patients studied. Maximal effects were observed three to five days following initiation of therapy. The largest increases in frequency of MN CD71+ (up to 25.9-fold) were observed in those patients exposed to anti-neoplastic drugs, presumably due to the systemic red marrow exposure provided by these agents. Taken together, these data support the hypothesis that the MN CD71+ endpoint represents a valuable biomarker of cytogenetic damage that does not require cell culture or microscopy-based scoring.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Dertinger¹,

Miller²,

Brewer³

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

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“…There might be several explanations to the difference that is observed in our study but not in studies by others: e.g., in comparison with the human lymphocytes, the life time of the studied cell population, the transferrinpositive erythrocytes, is very short and represents a very young population of erythrocytes in the peripheral blood. The formation of MN, monitored in this study, occurs in erythroblasts late in the maturation in bone marrow [15,16]. Furthermore, the use of a flow cytometer for the enumeration of MN, which enable a high number of analyzed cells, increases the sensitivity of the test.…”

Section: Discussionmentioning

confidence: 98%

“…Transferrin-positive immature peripheral blood reticulocytes (Trf-Ret) were enriched by magnetic separation, after which the cells containing MN (MN-Trf-Ret) were discriminated using RNA and DNA fluorescent dyes [15]. This method has been previously used in various human studies [9,[16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians

et al. 2014

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These data suggest that the vegetarian diet might be beneficial in lowering genomic instability in healthy individuals. The measured Hb adduct levels indicate that the total intake of acrylamide does not differ between the two studied groups and does not contribute to the observed difference in fMN, although an influence of the diet on the metabolic rates of acrylamide was indicated. In addition, the observed significant difference in the background fMN in the two groups demonstrated that the MN analysis method has a sensitivity applicable to the biomonitoring of human lifestyle factors.

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“…While the MN-RET endpoint has been studied extensively by radiation researchers, there has been relatively limited utilization of flow cytometric procedures for enumerating these events [14][15][19][20][21]. There is reason to believe that automated systems will become more widely utilized, as they are more objective by nature, and have the ability to score many times more cells compared with microscopy-based methods.…”

Section: Discussionmentioning

confidence: 99%

Reticulocyte and micronucleated reticulocyte responses to gamma irradiation: dose–response and time-course profiles measured by flow cytometry

Dertinger

Tsai

Nowak

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

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A flow cytometric, anti-CD71-based method was used to measure peripheral blood reticulocyte and micronucleated reticulocyte frequencies in response to 137 Cs total body irradiation (TBI). In three independent experiments, groups of five female C57BL/6N mice were irradiated at graded doses up to 3 Gy, and peripheral blood specimens were collected at 43 hrs post-irradiation. Whereas the frequency of reticulocytes declined over the range of doses studied, micronucleated reticulocyte incidence was observed to increase in a dose-dependent manner up to 1 Gy. At doses greater than approximately 1 Gy, micronucleated reticulocyte frequencies declined with increasing exposure. These responses were highly reproducible, with significant effects on reticulocyte and micronucleated reticulocyte frequencies observed for the lowest dose studied (0.125 Gy). A timecourse experiment was performed to test whether radiation-induced cell cycle delay may explain saturation of the micronucleated reticulocyte endpoint at doses > 1 Gy. For this experiment, groups of four female C57BL/6N mice were exposed to 1, 1.5, or 2 Gy TBI, and blood collection occurred at 12 hr intervals from 43 to 115 hrs post-exposure. Reduced reticulocyte frequencies were observed for each dose studied, and the recovery of reticulocytes was increasingly delayed with higher radiation doses. Maximal micronucleated reticulocyte frequencies were observed at 43 or 55 hrs, with progressively lower values at later time points. At no time did micronucleated reticulocyte frequencies induced by 1.5 or 2 Gy significantly exceed that observed for 1 Gy at 43 hrs. These timecourse data suggest that radiation-induced cell cycle delay cannot account for the micronucleated reticulocyte downturn phenomenon observed at doses greater than 1 Gy. An alternate hypothesis is discussed whereby apoptotic elimination of severely damaged bone marrow erythroid precursors plays a dominant role in saturating the radiation-induced micronucleated reticulocyte response observed for C57BL/6N mice.

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Evaluation of the reticulocyte micronucleus assay in patients treated with radioiodine for thyroid cancer

Cited by 39 publications

References 27 publications

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians

Reticulocyte and micronucleated reticulocyte responses to gamma irradiation: dose–response and time-course profiles measured by flow cytometry

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