2002 CTOS Annual Meeting Oral Presentations — Biology

DIFFERENTIAL EFFECTS OF THE RADIOPROTECTANT AMIFOSTINE ON EWING'S SARCOMA AND HUMAN MONOCYTES IN CULTURE
[Abstract ID: 46]

Category: Biology

Presentation: Oral

Authors: Bryan Margulies¹, Timothy A. Damron¹, Matthew J. Allen¹

Author Institutions: ¹SUNY Upstate Medical University at Syracuse, New York, United States

Presenter: Matthew J. Allen
allenm@mail.upstate.edu

Correspondent: Timothy A. Damron
tdamron@twcny.rr.com
Syracuse New York United States 13202
Ph: 315-464-4472
Fax: 315-464-4664

Objectives: Radioprotectants must be selectively radioprotectant, protecting normal cells at the expense of tumor cells. Such selectivity has not been established for sarcomas. The hypothesis investigated in this pilot was that amifostine alone would not promote proliferation of Ewing's sarcoma cells or human monocytes.

Methods: Amifostine at concentrations of 0, 0.5, 1, 2, 5, and 10 mM was administered to confluent TC-71 Ewing's sarcoma cells. At 6, 12, 24, and 72 hours following amifostine administration, MTT assays of cellular proliferation were performed. Clonogenicity assays of reproductive survival were also accomplished utilizing 0, 1, 5, and 10 mM concentrations of amifostine. Human monocytes were cultured from proximal femoral bone marrow aspirated during routine total hip procedures following IRB approved patient consent. These monocytes were similarly assayed following amifostine administration ANOVA was utilized with alpha 0.05.

Results: Amifostine was acutely toxic to TC-71 Ewing's sarcoma cells at 5-10 mM, moderately toxic at 2 mM, and mild to moderately toxic at 0.5 and 1 mM as manifested by the MTT assays. Clonogenicity assays on the amifostine treated TC-71 cells confirmed the observations made with the MTT assay. By contrast, human monocytes exhibited a consistent increase in proliferation following amifostine administration.

Conclusions: Amifostine has a cytotoxic effect on this Ewing's sarcoma cell line at clinically relevant concentrations (1-2 mM). By contrast, a proliferative effect of amifostine was observed in our human monocyte culture. These effects are promising and warrant further study of the putative differential radioprotective properties of amifostine in sarcomas.