The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure. Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro. Target concentrations of MIC were 2, 15, and 30 ppm (3 hr).Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)-or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm. Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 ± 0.4 ppm for 3 hr.At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels. However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater. A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a latereplicating Y chromosome.Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.
At 3, 6, and 24 h after acute treatment of BD2F1 mice with 3.3 mmol/kg of ethyl carbamate, blood was drawn and cultured for SCE analysis. After blood sampling, the same mice were infused with BrdUrd for simultaneous assessment of SCEs in bone marrow and alveolar macrophage cells. In bone marrow and alveolar macrophage cells, maximum SCE responses (24.1 +/- 4.3; 24.2 +/- 3.8, respectively) were observed at 3 h post-exposure. Decreased SCE frequencies were observed at each later time. Relative to a single (3.3 mmol/kg) acute treatment, multiple treatment (10 X 3.3 mmol/kg; every other day) did not produce significantly elevated SCE levels in bone marrow (18.3 +/- 1.5) and alveolar macrophage cells (22.2 +/- 5.8). By contrast, the maximum lymphocyte response (18.8 +/- 2.2), following a single acute injection, was observed at 6 h post-exposure. In addition, a considerable accumulation of SCE frequencies occurred in lymphocytes (27.3 +/- 3.4) following multiple injections of ethyl carbamate.
BrdU and BrdC have been employed as DNA labeling agents for differentiation of sister chromatids and for extension of sister chromatid exchange (SCE) methods to regenerating murine liver cells in vivo. Comparisons were made between bone marrow and liver cells isolated simultaneously from mice following DNA labeling with either BrdC or BrdU. Although the total mitotic yield of bone marrow cells was considerably greater than in liver, a higher percentage of second division metaphases was observed in liver cell preparations. The percentages of second division c-metaphase cells observed were 31.5% in bone marrow and 73% in liver cell preparations. Utilizing either BrdU or BrdC, no significant difference in percentage of second division metaphases was discerned. The number of spontaneous SCEs per cell was distributed according to the Poisson probability function. No significant differences in mean numbers of SCEs per cell were found in comparisons of bone marrow (1.40) and liver cells (1.65) or of cells which had incorporated BrdU or BrdC.
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