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Erschienen in: Strahlentherapie und Onkologie 3/2013

01.03.2013 | Original article

In vitro hypoxic cytotoxicity and hypoxic radiosensitization

Efficacy of the novel 2-nitroimidazole N,N,N-tris[2-(2-nitro-1H-imidazol-1-yl)ethyl]amine

verfasst von: M. Langenbacher, Dr. R.J. Abdel-Jalil, W. Voelter, M. Weinmann, S.M. Huber

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 3/2013

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Abstract

Background and purpose

Tumor hypoxia is a major problem in radiation therapy of solid tumors because of the radiosensitizing effect of oxygen. Nitroimidazole-containing compounds are oxygen mimetics accumulating in hypoxic tumor areas. However, the broad use of 2-nitroimidazoles as a hypoxic radiosensitizer is limited by their partially low efficacy and/or high neurotoxicity.

Materials and methods

Here, we characterized the in vitro hypoxic cytotoxicity and hypoxic radiosensitizing efficacy of N,N,N-tris [2-(2-nitro-1H-imidazol-1-yl)ethyl]amine (PRC) in a hypoxia-sensitive lymphoma and a hypoxia-resistant glioblastoma cell line by colony formation assay and flow cytometry.

Results

PRC exerted high hypoxic cytotoxic and radiosensitizing action on both cell lines at almost absent toxicity under normoxic conditions. In particular, under hypoxia, but not normoxia, PRC targeted the mitochondria resulting in oxidative stress, G2/M cell cycle arrest, and triggering of the intrinsic apoptosis pathway.

Conclusion

Our in vitro findings suggest that PRC might be a promising new 2-nitroimidazole for improving radiation therapy of hypoxic tumors in vivo.
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Metadaten
Titel
In vitro hypoxic cytotoxicity and hypoxic radiosensitization
Efficacy of the novel 2-nitroimidazole N,N,N-tris[2-(2-nitro-1H-imidazol-1-yl)ethyl]amine
verfasst von
M. Langenbacher
Dr. R.J. Abdel-Jalil
W. Voelter
M. Weinmann
S.M. Huber
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 3/2013
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-012-0273-2

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