Gliosarcoma Cell Death After Radiosurgery in a Rat Model

T. G. Psarros; B. Mickey; J. Gilio; J. Drees; K. Gall; D. Carlson; C. Giller; M. S. Willis

doi:10.1055/s-2004-830266

min - Minimally Invasive Neurosurgery, Table of Contents

Minim Invasive Neurosurg 2005; 48(3): 142-148
DOI: 10.1055/s-2004-830266

Original Article

Gliosarcoma Cell Death After Radiosurgery in a Rat Model

T. G. Psarros¹ , B. Mickey¹ , J. Gilio¹ , J. Drees¹ , K. Gall¹ , D. Carlson² , C. Giller¹ , M. S. Willis^2, ³

¹Department of Neurosurgery, University of Texas Southwestern, Dallas, Texas, USA
²Department of Surgery, University of Texas Southwestern, Dallas, Texas, USA
³Department of Pathology, University of Texas Southwestern, Dallas, Texas, USA

Abstract

Therapeutic radiation and subsequent detection of tumor cell death has been performed mainly in vitro systems, making it difficult to accurately characterize the mechanisms of tumor cell death after radiosurgery. To better characterize what occurs to glioma cells after radiation therapy, we developed a rat model using the 9L gliosarcoma cell line implanted reproducibly to the caudate nucleus in rats. After 1 Gy radiation, 9L tumors in vivo induced mainly necrosis (determined by trypan blue exclusion) of 10 - 74 % at 6 - 72 hours post-radiation. This is in contrast to a previous in vitro study which demonstrated that 18 Gy of radiation induces considerably less cell death as determined by trypan blue exclusion (approximately 20 - 25 % at 6 - 72 hours post-radiation). However, significant amounts of apoptosis were detected as early as 6 hours after radiation. Apoptosis determination was by annexin V (marker of early apoptosis) and propidium iodide (marker of membrane stability) staining followed by flow cytometry detection. When caspase 3 and caspase 8 enzymatic activities (mediators of apoptosis) were measured from freshly explanted tumor cells, peak activity was found 6 hours after 1 Gy radiation (p < 0.01). Taken together, these data indicate the presence of apoptosis early after radiation therapy (1 Gy) which progressed to necrosis in a unique in vivo model of gliosarcoma that may prove useful in determining new therapeutic approaches to radiation therapy and tumor cell biology.

Key words

9L gliosarcoma - radiosurgery - cell death - apoptosis

Full Text

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Tom G. Psarros,M. D.

Department of Neurosurgery · University of Texas Southwestern

5323 Harry Hines Blvd.

Dallas, TX 75390-885

USA

Email: tompsarros@aol.com