Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information. | |||||||
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Androgen manipulation alters oxidative DNA adduct levels in androgen-sensitive prostate cancer cells grown in vitro and in vivo.Pathak S, Singh R, Verschoyle RD, Greaves P, Farmer PB, Steward WP, Mellon JK, Gescher AJ, Sharma RA Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK. Intracellular reactive oxygen species (ROS) may cause oxidative DNA damage, resulting in the formation of adducts such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the cyclic pyrimidopurinone N-1, N(2) malondialdehyde-2'-deoxyguanosine (M(1)dG). These adducts have been associated with carcinogenesis, genomic instability and clonal evolution. We tested two hypotheses in human prostate cancer cells grown in vitro and in a xenograft model: (1) treatment of androgen-sensitive cells with DHT increases levels of oxidative DNA adduct levels; (2) flutamide, a competitive androgen receptor antagonist, prevents DHT-induced changes. Levels of M(1)dG and 8-oxo-dG adducts were determined by immunoslot blot and liquid chromatography-tandem mass spectrometry. M(1)dG and 8-oxo-dG levels were significantly higher than control levels in LNCaP cells exposed to supra-physiological concentrations (25-100 nM) of DHT (both P<0.05 by ANOVA). Flutamide pre-treatment completely prevented this increase. In the xenograft model, tumour levels of M(1)dG were decreased by 46% (P=0.001 by Mann-Whitney Test) in flutamide-treated animals compared to controls. The changes demonstrated suggest that oxidative DNA adducts may serve as biomarkers of the efficacy of androgen manipulation in chemoprevention trials. Published 11 February 2008 in Cancer Lett, 261(1): 74-83.
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