Giardia intestinalis: aphidicolin influence on the trophozoite cell cycle.
This study is a thorough examination of the effects of the DNA polymerase inhibitor aphidicolin on the nuclear cycle and cell cycle progression characteristics, as well as their reversibility, in Giardia intestinalis. Giardia trophozoites are arrested in the G1/S-junction after aphidicolin treatment according to their DNA content. However, cell growth continues and trophozoites arrested with aphidicolin resemble cells in the G2 phase and trophozoites in ageing cultures. Extensive treatment with aphidicolin causes side effects and we detected positive signals for phosphorylated histone H2A, which, in mammalian cells, is involved in a signalling pathway triggered as a reaction to double stranded DNA breaks. These results suggest that aphidicolin causes dissociation of the nuclear and cytoplasmic cycles, a phenomenon that has also been described for other inhibitors in mammalian cell lines. Thus, if aphidicolin is used for synchronization of Giardia trophozoites, this fact must be accounted for, and treatment with aphidicolin must be minimal.
Hofstetrová
Klára
K
3rd Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and University Hospital Bulovka, Czech Republic.
Uzlíková
Magdalena
M
Tůmová
Pavla
P
Troell
Karin
K
Svärd
Staffan G
SG
Nohýnková
Eva
E
D016590:Aphidicolin / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D019926:Cyclin B / Q000032:analysis; D004249:DNA Damage / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D016054:DNA, Protozoan / Q000096:biosynthesis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016829:Giardia lamblia / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008940:Mitotic Index; D019384:Nucleic Acid Synthesis Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D053058:Trophozoites / Q000166:cytology / Q000187:drug effects
D019926:Cyclin B; D016054:DNA, Protozoan; D004791:Enzyme Inhibitors; D006657:Histones; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; D001973:Bromodeoxyuridine