Studies on cell-cycle synchronization in the asexual erythrocytic stages of Plasmodium falciparum.
Multiplication of Plasmodium parasites within human erythrocytes is essential to malarial disease. The cell-division cycle of this organism, however, is still poorly understood. In other eukaryotes, various techniques for (apparent) cell-cycle synchronization have been used to shed light on the mechanisms involved in cell division and its control. Thus far there is no technique for cell-cycle synchronization (as opposed to selection of parasites of a limited age-range) in Plasmodium. We therefore investigated the possibility that inhibitors of DNA synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin-dependent kinases) could be used to synchronize P. falciparum cultures to a particular cell-cycle phase. Surprisingly, most of these compounds did not cause a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L-mimosine, did block development at the trophozoite-schizont transition (S or G2 phase). The block caused by the latter 2 inhibitors was reversible, suggesting that they might be used as synchronizing agents. However, a consideration of the perturbing effects of inhibitors and problems with 'batch' synchronization techniques in general lead us to believe that any results obtained using roscovitine- or L-mimosine-treated parasites may not be reflective of the normal cell cycle.
Naughton
J A
JA
Department of Microbiology, Moyne Institute of Preventive Medicine, University of Dublin, Trinity College, Dublin 2, Ireland.
Bell
A
A
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D016054:DNA, Protozoan / Q000096:biosynthesis / Q000187:drug effects; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008898:Mimosine / Q000494:pharmacology; D010274:Parasitology / Q000379:methods; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D052939:Schizonts / Q000187:drug effects / Q000254:growth & development; D053058:Trophozoites / Q000187:drug effects / Q000254:growth & development
D001562:Benzimidazoles; D016054:DNA, Protozoan; D011687:Purines; D000077546:Roscovitine; D008898:Mimosine; C017807:bisbenzimide ethoxide trihydrochloride