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Effect of post-exposure administration of keratinocyte growth factor (Palifermin) on radiation effects in oral mucosa in mice

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Abstract

Oral mucositis is a severe component of the acute radiation syndrome. The present study was initiated to determine the potential of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) to ameliorate oral mucositis in a mouse model after a single radiation exposure. A 3 × 3 mm2 area in the center of the lower tongue surface of C3H/Neu mice was irradiated with graded single doses of 25 kV X-rays. Acute mucosal ulceration was used as the quantal end-point for dose–response analyses. Palifermin was applied at a dose of 15 mg/kg on days 0, 1, 2, 3, 4 or 5. For comparison, three injections of 5 or 15 mg/kg on days 1–3 were administered. The ED50 (dose at which ulceration is expected in 50% of the animals) for irradiation alone was 11.6 ± 1.2 Gy. Mean latent time was 9.4 ± 0.2 days; mean ulcer duration was 2.8 ± 0.2 days. Single injections of rHuKGF did not result in a significant increase in isoeffective radiation doses at any of the administration days. However, the latent time to ulceration was significantly shortened by 1–2 days in all protocols. Repeated administration of rHuKGF (15 mg/kg) resulted a significant increase in ED50 to 16.8 ± 4.0 Gy (P = 0.0047); the mean latent time was 4.4 ± 0.9 days. Three injections of 5 mg/kg of Palifermin on days 1–3 yielded an ED50 of 19.4 ± 1.7 Gy. In this protocol, mean latent time was 6.6 ± 0.6 days. In conclusion, Palifermin has a potential to reduce the mucositis burden in patients after a single radiation exposure. Repeated injections are required. For three injections, a negative dose-effect of rHuKGF was observed. The optimum dose, number and timing of the administration require further investigation.

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Acknowledgments

This work was supported in part by AMGEN Inc. (Thousand Oaks, CA, USA). The authors are grateful to Mrs. K. Spekl and Mrs. D. Pfitzmann, for skilful assistance.

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Authors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307, Germany

    Yasemin Kiliç, Katja Rajewski & Wolfgang Dörr

  2. Experimentelles Zentrum, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Wolfgang Dörr

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  1. Yasemin Kiliç
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  2. Katja Rajewski
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  3. Wolfgang Dörr
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Correspondence to Wolfgang Dörr.

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Kiliç, Y., Rajewski, K. & Dörr, W. Effect of post-exposure administration of keratinocyte growth factor (Palifermin) on radiation effects in oral mucosa in mice. Radiat Environ Biophys 46, 13–19 (2007). https://doi.org/10.1007/s00411-006-0079-7

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  • DOI: https://doi.org/10.1007/s00411-006-0079-7

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