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Influence of clinically used antioxidants on radiation-induced expression of intercellular cell adhesion molecule-1
M Walther1, W Kaffenberger, D Van Beuningen
1Institute of Radiobiology, Federal Armed Forces Medical Academy, Munich, Germany.
Purpose:
The effects of antioxidants (N-acetyl-L-cysteine [NAC] and pyrrolidine dithiocarbamate [PDTC]) on radiation-induced ICAM-1 expression on human umbilical vein endothelial cells (HUVEC) were investigated.
Materials And Methods:
The expression of ICAM-1 on HUVEC was determined by flow cytometry up to 72 h after X-irradiation. Functional competence of induced ICAM-1 was assessed by adhesion experiments with human polymorphonuclear neutrophils on irradiated HUVEC.
Results:
Preincubation of cells with both or either NAC and PDTC was unable to reduce radiation-induced ICAM-1 expression on HUVEC. In fact, by themselves, these antioxidants induced a significant increase of ICAM-1 expression, which in comparison with a radiation dose of 7 Gy after 24h was nine times higher for PDTC, and more than double for NAC. Treatment with NAC clearly restrained TNF-alpha-induced ICAM expression on HUVEC, while preincubation of cells with PDTC showed synergistic effects.
Conclusions:
The role of reactive oxygen intermediates in signal transduction pathways leading to ICAM-1 expression should be investigated further. Furthermore, antioxidants may exert a pro-inflammatory role, as revealed by the induction of ICAM-1 expression on endothelial cells. The inhibition of TNF-alpha-induced ICAM-1 expression by NAC might have clinical implications because this substance is used as a radioprotector in radiotherapy.