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 pyrroli dine dithiocarbamate [PDTC]) on radiation-induced ICAM-1 expression on huma n 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 ind uced ICAM-1 was assessed by adhesion experiments with human polymorphonucle ar 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 themse lves, these antioxidants induced a significant increase of ICAM-1 expressio n, which in comparison with a radiation dose of 7 Gy after 24h was nine tim es higher for PDTC, and more than double for NAG. Treatment with NAC clearl y restrained TNF-alpha-induced ICAM expression on HUVEC, while preincubatio n of cells with PDTC showed synergistic effects. Conclusions: The role of reactive oxygen intermediates in signal transducti on pathways leading to ICAM-1 expression should be investigated further. Fu rthermore, antioxidants may exert a proinflammatory role, as revealed by th e induction of ICAM-I expression on endothelial cells. The inhibition of TN F-alpha-induced ICAM-1 expression by NAC might have clinical implications b ecause this substance is used as a radioprotector in radiotherapy.