Radioprotective effects of ATP in human blood ex vivo.
Damage to healthy tissue is a major limitation of radiotherapy treatment of cancer patients, leading to several side effects and complications. Radiation-induced release of pro-inflammatory cytokines is thought to be partially responsible for the radiation-associated complications. The aim of the present study was to investigate the protective effects of extracellular ATP on markers of oxidative stress, radiation-induced inflammation and DNA damage in irradiated blood ex vivo. ATP inhibited radiation-induced TNF-alpha release and increased IL-10 release. The inhibitory effect of ATP on TNF- alpha release was completely reversed by adenosine 5'-O-thiomonophosphate, indicating a P2Y(11) mediated effect. Furthermore, ATP attenuated radiation-induced DNA damage immediate, 3 and 6h after irradiation. Our study indicates that ATP administration alleviates radiation-toxicity to blood cells, mainly by inhibiting radiation-induced inflammation and DNA damage.
Swennen
Els L R
EL
Department of Epidemiology, NUTRIM Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Dagnelie
Pieter C
PC
Van den Beucken
Twan
T
Bast
Aalt
A
D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000328:Adult; D001790:Blood Physiological Phenomena / Q000187:drug effects* / Q000528:radiation effects*; D001798:Blood Proteins / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000008:administration & dosage
D001798:Blood Proteins; D016207:Cytokines; D011837:Radiation-Protective Agents; D000255:Adenosine Triphosphate; D004247:DNA