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-treated peripheral blood mononuclear cells (PBMC) from human subjects of different ages. The cytokine used, called K-7/D-6, is an IL-6 variant with increased in vivo and in vitro biological activity compared to the wild type molecule. Ku is the DNA-binding component of the DNA-dependent protein kinase (DNA-PK). It binds the ends of various types of DNA discontinuity and is involved in the repair of DNA breaks caused by V(D)J recombination, isotype switching, physiological oxidation reactions, ionizing radiation and some chemotherapeutic drugs. The ku-dependent repair process, called non-homologous end joining, is the main DNA double strand break repair mechanism in irradiated 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 irradiated 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.
Frasca
D
D
Laboratory of Immunology, AMB-PRO-TOSS, ENEA C.R. Casaccia, Via Anguillarese 301, 00060 S. Maria di Galeria, Rome, Italy. frasca@casaccia.enea.it
Barattini
P
P
Tocchi
G
G
Guidi
F
F
Scarpaci
S
S
Guidi
L
L
Bartoloni
C
C
Errani
A
A
Costanzo
M
M
Doria
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D034961:Antigens, Nuclear; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004265:DNA Helicases; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D000072200:Ku Autoantigen; D009000:Monocytes / Q000502:physiology* / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000378:metabolism; D014965:X-Rays
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen