Guanosine induces necrosis of cultured aortic endothelial cells.
We have observed that treatment of cultured bovine aortic endothelial (BAE) cells with guanosine can inhibit the proliferation and viability of the cells. The addition of 500 mumol/L guanosine to the medium resulted in approximately 90% inhibition of cell proliferation. It also changed the morphology of BAE cells from having a small cobblestone-like appearance to a giant pancake-like morphology. At a concentration range of 1 to 2.5 mmol/L, guanosine inhibited the viability of quiescent BAE cells. Incubation of the cells with 2 mmol/L guanosine for 24 hours maximally induced the loss of cell viability by approximately 80%. We also compared the effects of different nucleosides on the proliferation and viability of BAE cells and found that at appropriate concentration ranges, only guanosine was able to inhibit the proliferation and viability of the cells. To assess the mechanism that mediates the cytotoxicity of guanosine, we analyzed the degradation pattern of DNA in guanosine-treated cells and found that random DNA degradation occurred in the cells. Thus, we suggest that treatment of BAE cells with guanosine induced cell necrosis.
Han
Z
Z
Section of Molecular, Cellular, and Development Biology, Brown University, Providence, Rhode Island 02912.
Wyche
J H
JH
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006151:Guanosine / Q000494:pharmacology*; D009336:Necrosis
D006151:Guanosine; D004247:DNA