Résumé
The nuclear factor κB (NF-κB) is involved in T cell activation 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 trigger activation of NF-κB. We now show that a series of topoisomerase poisons (actinomycin D, camptothecin, daunomycin and etoposide) also activate NF-κB (NFKB1/RelA dimer) in ACH-2 and CEM cells. This activation 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 the formation of single-and double-strand breaks in DNA, these lesions might be capable of triggering NF-kB activation. Indeed, DNA damaging agents generating adducts (trans-platin and 4-nitroquinoline 1-oxide) and/or crosslinks in DNA (cis-platin and mitomycin C) do not or only weakly activate NF-κB in T cell lines.