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Sherilyn A. Gordon, MD; Rosemary A. Hoffman, BS; Richard L. Simmons, MD; Henri R. Ford, MD

Arch Surg. 1997;132(12):1277-1282.

Abstract
Objectives
To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection.

Design
Thymocytes from BALB/c mice or Tlymphocyte clones were incubated at 43°C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, box, and bcl-2 expression was analyzed at various times by the Western blot method.

Results
Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T-cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly up-regulated box. The expression of p53 peaked at 4 hours and preceded maximal box induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased box levels. Levels of bcl-2 were unaffected.

Conclusions
Our data show that HSP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and box expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.

Arch Surg. 1997;132:1277-1282

Author Affiliations
From the Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa.

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