Micronuclei Elimination in MCF-7 Human Breast Adenocarcinoma Cells

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Abstrac

t—Recent literature data have demonstrated that cells are able to eliminate micronuclei. Induction of micronuclei with antitubulin agents is widely used in antitumor therapy and elimination of micronuclei presumably facilitates the survival of tumor cells during therapy. In this regard, the investigation of micronuclei elimination has both fundamental and practical significance. In the present study, we show presence of two subpopulations of micronuclei (small single and large multiple micronuclei) in MCF-7 cells (human breast adenocarcinoma cell line, p53+) both in control and after paclitaxel treatment. Each of these subpopulations obviously has different mechanisms of formation. It has been shown that the lysosomal compartment can be involved in the elimination of micronuclei (for small micronuclei). It has been found that elimination of a micronucleus is a rare phenomenon. Most micronuclei were preserved, but the micronuclei could have morphological defects. We described different defects in a micronuclear envelope: lack of peripheral heterochromatin, swelling of the perinuclear space, micronuclear membrane breaks, and complete or partial absence of a nuclear lamina. We found the presence of p53-negative micronuclei. Lack of p53 activation is more characteristic for small single micronuclei. The obtained data allow us to conclude that the elimination of micronuclei cannot have a significant impact on the results of therapy. However, there is a danger of micronuclear cells progressing through the cell cycle (primarily for cells with small single micronuclei).