Effect of microcystin-LR and cyanobacterial extract from Polish reservoir of drinking water on cell cycle progression, mitotic spindle, and apoptosis in CHO-K1 cells.

Abstract

Microcystin-LR is a cyanobacterial toxin possessing a potent tumor-promoting activity mediated through inhibition of protein phosphatases PP1 and PP2A. Because these enzymes are involved in fundamental cell processes, we decided to examine the influence of microcystin-LR on cell cycle progression, onset of anaphase, segregation of chromosomes by the mitotic spindle, and apoptosis in Chinese hamster ovary (CHO-K1) cells. Cells were incubated with 25, 50, and 100 microM of pure microcystin-LR and a cyanobacterial extract for 14, 18, and 22 h. Giemsa staining of cells treated with these toxins revealed a dose- and time-dependent increase of mitotic indices, accumulation of abnormal G(2)/M figures with hypercondensed chromosomes, abnormal anaphases with defective chromosome separation, and polyploid cells. Because spindle checkpoint is a fundamental regulatory mechanism that assures the onset of anaphase and subsequent exit from mitosis, we examined the spindle organization in microcystin-treated cells. The majority of the mitotic cells showed monopolar and multipolar mitotic spindles (multiple asters). Microtubule bundles were present in interphase cells. Our results indicate that microcystin-LR induces apoptosis and necrosis in a dose- and time-dependent manner and that the frequency of dead cells cells is positively correlated with the frequency of polyploid cells.

• Authors: Anna Lankoff, Anna Banasik, Guenter Obe, Marta Deperas, Konrad Kuzminski, Malgorzata Tarczynska, Tomasz Jurczak, Andrzej Wojcik
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 189 Issue 3 Pg. 204-13 (Jun 15 2003) ISSN: 0041-008X [Print] United States
• PMID: 12791305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Marine Toxins
• Microcystins
• Peptides, Cyclic
• cyanoginosin LR

Topics

• Animals
• Apoptosis (drug effects, physiology)
• CHO Cells
• Cell Cycle (drug effects, physiology)
• Cricetinae
• Cyanobacteria (isolation & purification)
• Marine Toxins
• Microcystins
• Peptides, Cyclic (isolation & purification, pharmacology)
• Poland
• Spindle Apparatus (drug effects, physiology)
• Water Supply (analysis)