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

Abstract

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.

Induction and assessment of persistent radioresistance in murine leukocytes in vivo

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In VivoGenotoxicity and Cytotoxicity Kinetics of Trimethoprim Sulfamethoxazole in Well-nourished and Undernourished Young Rats

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“…This precision allowed the sample to be deposited in the center of the fixation tube within a short distance of the vortex produced by an electric mixer in −75°C methanol. The use of this dispositive method enabled the correct fixation of 100% of the samples and an analysis of 90% of the cells with minimal number of cell aggregates (Cruz‐Vallejo et al ., 2019). The fixed samples were immediately stored at −75°C until labeling and staining for analysis.…”