The alpha, beta, gamma, delta-unsaturated aldehyde 2-trans-4-trans-decadienal disturbs DNA replication and mitotic events in early sea urchin embryos.
The polyunsaturated aldehydes are highly reactive products of fatty acid peroxidation and combustion of organic materials, and they have been documented to have diverse cyctotoxic and genotoxic effects. The alpha,beta,gamma,delta-unsaturated aldehyde 2-trans-4-trans-decadienal is produced by marine microalgae, and it is known to inhibit cell proliferation and induce apoptosis in several different cell types. However, the molecular basis for the cell cycle arrest is not fully understood. We used sea urchin embryos to examine how some of the key events of the mitotic cell division were influenced by this polyunsaturated aldehyde. We found that cell divisions in embryos of Sphaerechinus granularis were inhibited by 2-trans-4-trans-decadienal in a dose dependent manner with an EC50 of 1.3 microM. Mitotic events in the nondividing eggs were characterized using immunofluorescent staining. DNA labelling revealed that pronuclear migration was inhibited, and a total absence of incorporation of the DNA-base analogue 5-bromo-2-deoxyuridine indicated that no DNA replication had occurred. Staining of alpha-tubulin subunits showed that tubulin-polymerization was disrupted and aberrations were induced in mitotic spindles. Furthermore, we monitored the activity of the G2-M promoting complex cyclin B-Cdk1 in newly fertilized sea urchin eggs, and found that this complex was not activated in embryos treated with 2-trans-4-trans-decadienal despite the accumulation of cyclin B.
Hansen
Espen
E
Department of Aquatic Biosciences, NFH, University of Tromsø, N-9037, Norway. espenh@nfh.uit.no
Even
Yasmine
Y
Genevière
Anne-Marie
AM
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000963:Antimetabolites; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D019926:Cyclin B / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000378:metabolism; D007202:Indicators and Reagents; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008938:Mitosis / Q000187:drug effects*; D012617:Sea Urchins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects
D000447:Aldehydes; D000963:Antimetabolites; D002843:Chromatin; D019926:Cyclin B; D007202:Indicators and Reagents; C057349:2,4-decadienal; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D001973:Bromodeoxyuridine