Kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in vivo by aneuploidogens

Morales-Ramı́rez, P.; Vallarino-Kelly, T.; Cruz-Vallejo, Virginia

doi:10.1016/j.mrgentox.2004.09.006

Cited by 18 publications

(17 citation statements)

References 11 publications

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“…In the cells with BrdU‐substituted DNA, three peaks were observed after irradiation. The first peak was small and could be explained by the previously reported aneuploidogenic effect of radiation [Hande et al ], in agreement with our previous studies in which the micronuclei induced by aneuploidogens appear early [Morales‐Ramírez et al ]. The second peak was lower in terms of the area beneath the curve than that induced in BrdU unsubstituted DNA, but the results were not statistically significant and probably represent the breaks induced by debromination of the incorporated BrdU [Cecchini et al ].…”

Section: Discussionsupporting

confidence: 88%

In vivo Characterization of the Radiosensitizing Effect of a Very Low Dose of BrdU in Murine Cells Exposed to Low‐Dose Radiation

Cruz-Vallejo

Ortiz-Muñiz

Vallarino-Kelly

et al. 2019

Environ and Mol Mutagen

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The aim of the present study was to characterize the in vivo radiosensitizing effect of a very low dose of bromodeoxyuridine (BrdU) in mice exposed to low‐dose radiation by establishing the following: (1) the radiosensitizing effect during DNA synthesis using single‐cell gel electrophoresis (SCGE) in murine bone marrow cells, and (2) the number and timing of the mechanisms of genotoxicity and cytotoxicity, as well as the correlation of both end points, using flow cytometry analysis of the kinetics of micronucleus induction in reticulocytes. Groups of mice received intraperitoneal injections of 0.125 mg/g of BrdU 24 h prior to irradiation with 0.5 Gy of 60Co gamma rays. DNA breaks measured using SCGE were determined at 30 min after exposure to radiation. The kinetics of micronucleated reticulocyte (MN‐RET) induction was determined every 8 h after irradiation up to 72 h. The results from both experimental models indicated that low‐level BrdU incorporation into DNA increased the sensitivity to 0.5 Gy of radiation, particularly in the S phase. The formation of micronuclei by gamma rays was produced at three different times using two main mechanisms. In the BrdU‐substituted cells, the second mechanism was associated with a high cytotoxic effect that was absent in the irradiated BrdU‐unsubstituted cells. The third mechanism, in which micronucleus formation was increased in irradiated substituted cells compared with the irradiated nonsubstituted control cells, was also related to an increase in cytotoxicity. Environ. Mol. Mutagen. 60:534–545, 2019. © 2019 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 88%

In vivo Characterization of the Radiosensitizing Effect of a Very Low Dose of BrdU in Murine Cells Exposed to Low‐Dose Radiation

Cruz-Vallejo

Ortiz-Muñiz

Vallarino-Kelly

et al. 2019

Environ and Mol Mutagen

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“…For instance, some vinca alkaloids block cell division immediately, while vinblastine and vincristine cause a delay after exposure, although producing a higher maximal velocity (Morales-Ramirez et al, 2004). The induction of MN by colchicine also occurs rapidly; MNPCE appeared in blood stream almost at the same time as after exposure to gamma-rays (Vallarino-Kelly and Morales-Ramirez, 2001).…”

Section: Micronuclei and Genotoxic Agentsmentioning

confidence: 99%

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Luzhna¹,

Kathiria²,

Kovalchuk³

2013

Front. Genet.

359

203

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Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. MN can be induced by defects in the cell repair machinery and accumulation of DNA damages and chromosomal aberrations. A variety of genotoxic agents may induce MN formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of MN formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to MN formation due to single gene polymorphisms is discussed. The importance of rapid MN scoring with respect to the cytokinesis-block micronucleus assay is also evaluated.

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“…43 The aneugenic effects of paclitaxel can easily be compared to those induced by other tubulin-binding agents such as vinca alkaloids. Different studies demonstrated that vinblastine, [44][45][46] vincristine, 47,48 and vindesine 49 increased the frequency of MNE from the blood. Vinca alkaloids are known to be essentially aneugenic compounds despite a slightly different mechanism of action compare to taxanes.…”

Section: Discussionmentioning

confidence: 99%

“…At µM levels, vinca alkaloids act by inducing microtubule disassembly; however, it is important to note that at nM levels, taxanes and vinca alkaloids act similarly by inhibiting microtubule dynamics. 50 On the other hand, higher doses of vinblastine and vincristine resulted in a dose-dependent increase in the frequency of MNE and could induce a long lasting aneugenic effect, probably related to the accumulation of vinca alkaloids that are either free or associated to tubulin 44,45 . The dose response relationship of paclitaxel with MNE frequencies was not determined in our study and thus these experiments are needed.…”

Section: Discussionmentioning

confidence: 99%

“…47,48 Moreover, this drug is an active component of polychemotherapy schedules known to induce secondary malignancies. 24,45 However, a direct relationship between vincristine administration and increased incidence of secondary malignancies was never found. Here, we demonstrate that MNE frequencies were increased after paclitaxel treatment compared to the control group.…”

confidence: 99%

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Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

Galmarini

Bouchet²,

Falette³

et al. 2007

Cancer Biology & Therapy

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ABBreViAtioNs MNE ACKNowLedGeMeNtsBenjamin Bouchet is a recipient of a "Foundation pour la Recherche Medicale" grant. ABstrACtWe investigated the potential in vivo aneugenic effects associated with paclitaxel treatment. For this purpose, we treated female nude mice with paclitaxel using doses equivalent to those used in weekly schedules at the clinical level (three cycles of 30 mg/kg/week for three consecutive weeks followed by one resting week). We then evaluated the frequencies of micronucleated erythrocytes (MNE) in peripheral blood using the acridine orange micronucleus assay. The frequency of MNE was evaluated after 24 h and 168 h of administration of the last dose of each paclitaxel cycle (STA mice group) as well as after one year of the first dose of treatment (LTA mice group). We also analyzed the cytology of peripheral blood and bone marrows obtained from these mice at each time period. In the STA mice group, three cycles of paclitaxel induced a 2.4-fold increase in MNE frequencies compared to the control group (p < 0.01). This effect was observed after 24 h of the last dose of each chemotherapy cycle and persisted at least for 168 h. In the LTA mice group, paclitaxel-treated mice presented a 1.8-fold increase in the MNE frequency (p = 0.01) indicating that paclitaxel-induced MNE increase lasted for at least one year. Although the appearance of micronuclei in erythrocytes and granulocytes in peripheral blood and bone marrow cytological smears, there was no evidence of myeloproliferative disease. The present data therefore indicate an aneugenic potential of paclitaxel for humans, which should be considered in the risk-benefit analysis of its increasing clinical use.

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Kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in vivo by aneuploidogens

Cited by 18 publications

References 11 publications

In vivo Characterization of the Radiosensitizing Effect of a Very Low Dose of BrdU in Murine Cells Exposed to Low‐Dose Radiation

In vivo Characterization of the Radiosensitizing Effect of a Very Low Dose of BrdU in Murine Cells Exposed to Low‐Dose Radiation

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

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