title: Dramatic increase in oxidative stress in carbon-irradiated normal human skin fibroblasts.
abstract: Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D₀ (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D(10%) (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D(0%) (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this discrepancy between the two types of radiation should be investigated.
authors.affiliation: SAPHYN (Santé Physique Nucléaire), ARCHADE (Advanced Resource Centre for Hadrontherapy in Europe) Program, Caen, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Laurent
authors.affiliation: SAPHYN (Santé Physique Nucléaire), ARCHADE (Advanced Resource Centre for Hadrontherapy in Europe) Program, Caen, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Leduc
authors.affiliation: ABTE (Aliments, Bioprocédés, Toxicologie, Environnements), EA4651, Université de Caen-Basse Normandie, Caen, France ; CLCC (Centre de Lutte Contre le Cancer) François Baclesse, Caen, France.
authors.forename: Ivannah
authors.initials: I
authors.lastname: Pottier
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), U1086 Cancer et Préventions, Université de Caen-Basse Normandie, Caen, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Prévost
authors.affiliation: ABTE (Aliments, Bioprocédés, Toxicologie, Environnements), EA4651, Université de Caen-Basse Normandie, Caen, France ; CLCC (Centre de Lutte Contre le Cancer) François Baclesse, Caen, France.
authors.forename: François
authors.initials: F
authors.lastname: Sichel
authors.affiliation: LARIA (Laboratoire d'Accueil et de Recherche avec les Ions Accélérés), CEA (Commissariat à l'Energie Atomique) - DSV (Direction des Sciences du Vivant) - IRCM (Institut de Radiobiologie Cellulaire et Moléculaire), Caen, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Lefaix
mesh_terms: D000704:Analysis of Variance; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000528:radiation effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology* / Q000528:radiation effects; D012867:Skin / Q000166:cytology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014964:X-Ray Therapy
chemical_list: D016207:Cytokines; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione