Aluminum effects on growth of brain microvessel endothelial cells in primary culture.
Aluminum salts have been shown to stimulate 3H-thymidine incorporation in primary cultures of bovine brain microvessel endothelial cells (BMECs). Aluminum chloride or sulfate salts in concentrations between 0.01 to 100 microM were, in general, most effective in stimulation of thymidine uptake by BMECs with maximal effects observed after a 24 hour exposure to the metal. Concentrations of aluminum salts greater than 100 microM inhibited thymidine incorporation. Cell numbers were not affected by exposure to concentrations of the aluminum salts less than approximately 100 microM. Concentrations producing half-maximal stimulation of BMEC thymidine incorporation were approximately, 0.3 microM and 0.5 microM, for aluminum chloride and aluminum sulfate, respectively. These findings indicate that BMECs are sensitive to lower concentrations of aluminum salts than other mammalian cell types. Hydroxyurea completely inhibited thymidine incorporation into BMECs in the presence and absence of aluminum suggesting that thymidine incorporation into BMECs is representative of DNA synthesis. Endothelial cell growth factor (ECGF) stimulated both increased DNA synthesis and BMEC cell numbers in the primary culture system. Aluminum had only slight effects on DNA synthesis in endothelial cell growth factor stimulated BMECs. In contrast to ECGF, aluminum then, appears to provide a stimulus for DNA synthesis but not subsequent mitosis in BMECs. Results from this study are consistent with previous studies in other cell types and with current knowledge of the effects of aluminum on the blood-brain barrier in vivo.
Audus
K L
KL
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence 66045.
Holthaus
S R
SR
van Bree
J M
JM
Shinogle
J A
JA
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006918:Hydroxyurea / Q000633:toxicity; D008833:Microcirculation; D013936:Thymidine / Q000378:metabolism
D000535:Aluminum; D013936:Thymidine; D006918:Hydroxyurea