Influence of clinically used antioxidants on radiation-induced expression of intercellular cell adhesion molecule-1 on HUVEC

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 72h 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 7Gy 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 proinflammatory 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.