Methyl tert butyl ether is anti-angiogenic in both in vitro and in vivo mammalian model systems
Article first published online: 8 MAR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 8, pages 820–827, August 2013
How to Cite
Kozlosky, J., Bonventre, J. and Cooper, K. (2013), Methyl tert butyl ether is anti-angiogenic in both in vitro and in vivo mammalian model systems. J. Appl. Toxicol., 33: 820–827. doi: 10.1002/jat.2737
- Issue published online: 21 JUN 2013
- Article first published online: 8 MAR 2012
- Manuscript Accepted: 14 JAN 2012
- Manuscript Revised: 5 JAN 2012
- Manuscript Received: 29 SEP 2011
- methyl-tertiary butyl ether;
- endothelial cells;
- developmental study
Methyl-tertiary butyl ether (MTBE), a well known gasoline oxygenate, and US Food and Drug Administration approved gallstone treatment, has been previously shown to specifically target teleost embryonic angiogenesis. The studies reported here were to determine whether similar vascular disrupting effects occur in higher vertebrate models. Rat brain endothelial cells were isolated and allowed to form microcapillary-like tubes on Matrigel. MTBE (0.34–34.0 mm) exposure resulted in a dose-dependent reduction of tube formation, with the LOAEL at 0.34 mm, while MTBE's primary metabolite, tertiary butyl alcohol had no effect on tube formation. HUVECs, a primary cell line representing macrovascular cells, were able to form tubes on Matrigel in the presence of MTBE (1.25–80 mm), but the tubes were narrower than those formed in the absence of MTBE. In a mouse Matrigel plug implantation assay, 34.0 mm MTBE completely inhibited vessel invasion into plugs containing endothelial cell growth supplement (ECGS) compared with control plugs with ECGS alone. When timed-pregnant Fisher 344 rats were gavaged with MTBE (500–1500 mg kg−1) from day 6 of organogenesis through 10 days post-parturition, no organ toxicity or histological changes in pup vasculature were observed. Results of the in vitro cell culture studies show that MTBE is anti-angiogenic at mm concentrations and has potential use as an anti-angiogenic treatment for solid tumors with minimal toxicity. Copyright © 2012 John Wiley & Sons, Ltd.