TOPOISOMERASE POISONS ACTIVATE THE TRANSCRIPTION FACTOR NF-KAPPA-B INACH-2 AND CEM CELLS

The nuclear factor kappa B (NF-kappa B) is involved in T cell activati on and enhances HIV-1 gene expression. It is activated in response to numerous stimuli, including oxidative stress. Oxidative stress damages membrane lipids, proteins and nucleic acids. We have shown previously that oxidative DNA damage generated by photosensitization could trigg er activation of NF-kappa B. We now show that a series of topoisomeras e poisons (actinomycin D, camptothecin, daunomycin and etoposide) also activate NF-kappa B (NFKB1/RelA dimer) in AGH-2 and CEM cells. This a ctivation is inhibited by pyrrolidine dithiocarbamate. In ACH-2 cells latently infected by HIV-1, camptothecin, daunomycin and etoposide are able to enhance virus production. Since topoisomerase poisons cause t he formation of single- and double-strand breaks in DNA, these lesions might be capable of triggering NF-kappa B activation. Indeed, DNA dam aging agents generating adducts (trans-platin and 4-nitroquinoline 1-o xide) and/or crosslinks in DNA (cisplatin and mitomycin C) do not or o nly weakly activate NF-kappa B in T cell lines.