The a,b,g,q-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 theyhavebeendocumented tohavediverse cyctotoxic andgenotoxic effects. The a,b,g,d-unsaturated aldehyde 2-trans-4-trans-decadienal is produced bymarinemicroalgae, 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.Weusedseaurchinembryos toexaminehowsomeof 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 mM.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 a-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.