Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro

Erin Cohen; Stefanie Pena; Christine Mei; Olena Bracho; Brian Marples; Nagy Elsayyad; Stefania Goncalves; Michael Ivan; Paula V. Monje; Xue-Zhong Liu; Cristina Fernandez-Valle; Fred Telischi; Christine T. Dinh

doi:10.1055/s-0040-1722283

Journal of Neurological Surgery Part B: Skull Base, Inhaltsverzeichnis

J Neurol Surg B Skull Base 2022; 83(03): 228-236
DOI: 10.1055/s-0040-1722283

Original Article

Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro

Erin Cohen

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Stefanie Pena

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Christine Mei

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Olena Bracho

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Brian Marples

²Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Nagy Elsayyad

²Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Stefania Goncalves

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Michael Ivan

³Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Paula V. Monje

⁴Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, United States

⁵Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States

,

Xue-Zhong Liu

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Cristina Fernandez-Valle

⁶Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Miami, Florida, United States

,

Fred Telischi

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

,

Christine T. Dinh

¹Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States

› Institutsangaben

Abstract

Objectives Vestibular schwannomas (VS) are intracranial tumors, which are caused by NF2 gene mutations that lead to loss of merlin protein. A treatment for VS is stereotactic radiosurgery, a form of radiation. To better understand the radiobiology of VS and radiation toxicity to adjacent structures, our main objectives were (1) investigate effects of single fraction (SF) radiation on viability, cytotoxicity, and apoptosis in normal Schwann cells (SCs) and merlin-deficient Schwann cells (MD-SCs) in vitro, and (2) analyze expression of double strand DNA breaks (γ-H2AX) and DNA repair protein Rad51 following irradiation.

Study Design This is a basic science study.

Setting This study is conducted in a research laboratory.

Participants Patients did not participate in this study.

Main Outcome Measures In irradiated normal SCs and MD-SCs (0–18 Gy), we measured (1) viability, cytotoxicity, and apoptosis using cell-based assays, and (2) percentage of cells with γ-H2AX and Rad51 on immunofluorescence.

Results A high percentage of irradiated MD-SCs expressed γ-H2AX, which may explain the dose-dependent losses in viability in rodent and human cell lines. In comparison, the viabilities of normal SCs were only compromised at higher doses of radiation (>12 Gy, human SCs), which may be related to less Rad51 repair. There were no further reductions in viability in human MD-SCs beyond 9 Gy, suggesting that <9 Gy may be insufficient to initiate maximal tumor control.

Conclusion The MD-SCs are more susceptible to radiation than normal SCs, in part through differential expression of γ-H2AX and Rad51. Understanding the radiobiology of MD-SCs and normal SCs is important for optimizing radiation protocols to maximize tumor control while limiting radiation toxicity in VS patients.

Keywords

radiobiology - Schwann cells - radiation - DNA damage - DNA repair - merlin-deficient - vestibular schwannoma

Volltext

Referenzen

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