TY - JOUR TI - Isotretinoin therapy induces DNA oxidative damage AU - Georgala, S AU - Papassotiriou, L AU - Georgala, C AU - Demetriou, E and AU - Schulpis, KH JO - Clinical Chemistry and Laboratory Medicine (CCLM) PY - 2005 VL - 43 TODO - 11 SP - 1178-1182 PB - Walter de Gruyter GmbH SN - null TODO - 10.1515/CCLM.2005.204 TODO - cystic acne; DNA damage; free radicals; 8-hydroxy-2-desoxyguanosine (8-OhdG); isotretinoin TODO - Background: Isotretinoin (Iso) is currently indicated for the treatment of cystic acne (CA) and is related to marked teratogenicity. Aim: The aim of the study was to evaluate the relationship between total antioxidant status (TAS) and a serum marker of DNA oxidative damage, 8-hydroxy-2-desoxyguanosine (8-OHdG), in patients on Iso treatment. Patients and methods: Patients with CA (n=18) were evaluated before and 45 days after Iso (0.5 mg/kg per day) treatment and non-diseased controls (n = 22) were tested only once. Plasma TAS levels and 8-OHdG were measured spectrophotometrically and with an immunoassay, respectively. Liver biochemical parameters and muscle enzymes were measured on a blood chemistry analyzer. Results: TAS levels were significantly (p < 0.0001) lower in patients before treatment (921 +/- 124 mu mol/L) compared with those after treatment (1335 +/- 93 mu mol/L) and in controls (1536 +/- 126 mu mol/L). In contrast, 8-OHdG serum levels were two-fold higher in patients after treatment (0.21 +/- 0.03 ng/mL) than before treatment (0.11 +/- 0.02 ng/mL) and three-fold higher than in controls (0.07 +/- 0.01 ng/mL;p < 0.0001). Negative correlations were found between TAS and 8-OHdG (r=-0.754, p < 0.0001) in patients before therapy and positive correlations were found between creatine kinase (CK) and 8-OHdG (r=0.488, p < 0.001) and liver enzymes after Iso treatment. Conclusions: High serum levels of 8-OHdG in patients on Iso therapy may be due to a direct effect of Iso on liver, muscle and skin epidermal cells. Regular evaluation of 8-OHdG in sera of patients, especially of women of reproductive age, on Iso treatment could be a sensitive follow-up biomarker of DNA oxidation. ER -