Modulation of X-ray-induced damage recognition and repair in ageing human peripheral blood mononuclear cells by an interleukin-6-type cytokine

We have investigated the effects of an interleukin (IL)-6-type cytokine on the DNA-binding activity of ku and on unscheduled DNA repair in X-ray-treat ed peripheral blood mononuclear cells (PBMC) from human subjects of differe nt ages. The cytokine used, called K-7/D-6, is an IL-6 variant with increas ed in vivo and in vitro biological activity compared to the wild type molec ule. Ku is the DNA-binding component of the DNA-dependent protein kinase (D NA-PK). It binds the ends of various types of DNA discontinuity and is invo lved in the repair of DNA breaks caused by V(D)J recombination, isotype swi tching, physiological oxidation reactions, ionizing radiation and some chem otherapeutic drugs. The ku-dependent repair process, called non-homologous end joining, is the main DNA double strand break repair mechanism in irradi ated mammalian cells. Results show that K-7/D-6 significantly increases DNA -binding activity of ku in irradiated PBMC from young but not from elderly subjects. However, K-7/D-6 is able to induce unscheduled DNA repair in irra diated PBMC from both young and elderly subjects. These effects of K-7/D-6 are relevant to the mechanisms of the cellular response to DNA damage. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.