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Cell culture density dependent toxicity and chromatin changes upon cadmium treatment in murine pre-B-cells

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Abstract

Murine pre-B-cells grown in the presence of lower (1 μM) or higher (5 μM) concentration of cadmium chloride were separated into 13 fractions by centrifugal elutriation. The rate of DNA synthesis after cadmium treatment determined in permeable cells was dependent on cell culture density during cadmium treatment. Cell cycle analysis revealed a shift in the profile of DNA synthesis from replicative to repair DNA synthesis upon cadmium treatment. The study of the relationship between cell culture density and cell diameter at lower and higher cell densities in the presence of 1 μM cadmium chloride concentration showed that a. at 5×105 cell/ml or lower densities cells were shrinking indicating apoptotic changes, b. at higher cell culture densities the average cell size increased, c. the treatment of cells with low CdCl2 concentration (1 μM) at higher cell culture density (>5×105 cell/ml) did not change significantly the average cell diameter. At 5 μM cadmium concentration and higher cell culture densities (>5×105 cell/ml) the average cell size decreased in each elutriated fraction. Most significant inhibition of cell growth took place in early S phase (2.0–2.5 C value). Apoptotic chromatin changes in chromatin structure after cadmium treatment were seen as large extensive disruptions, holes in the nuclear membrane and stickiness of incompletely folded chromosomes.

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Acknowledgments

This work was supported by the OTKA grant T042762 (G.B.). This research was supported in part by the VA Merit Review grant and the DK58324-01A1 grant from the National Institutes of Health (A.G.B.).

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Correspondence to Gaspar Banfalvi.

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Banfalvi, G., Ujvarosi, K., Trencsenyi, G. et al. Cell culture density dependent toxicity and chromatin changes upon cadmium treatment in murine pre-B-cells. Apoptosis 12, 1219–1228 (2007). https://doi.org/10.1007/s10495-006-0045-5

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