RAT VENTRAL PROSTATE CYTOSOLIC XANTHINE OXIDASE MEDIATED METABOLISM OF ACETALDEHYDE TO ACETYL RADICALS

G.D. CASTRO; M.H. COSTANTINI; M.E. MACIEL; J.A. CASTRO

Washington DC

Conferencia; Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective - Launch Conference; 2007

World Cancer Research Foundation - American Institute for Cancer Research

Repetitive alcohol drinking is known to lead to deleterious effects on prostate epithelial cells from humans and experimental animals. The understanding of the mechanisms of these alcohol-induced effects is relevant to intraprostatic ethanol treatment of benign prostatic hyperplasia and to shed some light into the conflictive results linking alcohol consumption to prostate cancer. In previous studies from our laboratory we provided evidence about the presence in the rat ventral prostate of cytosolic and microsomal pathways of metabolism of ethanol to acetaldehyde and 1-hydroxyethyl radical and about the poor to null presence of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde accumulation in prostate tissue and oxidative stress promotion were also observed. In the present study we report that the ventral prostate cytosolic fraction xanthine oxidoreductase is able to metabolize acetaldehyde to acetyl radical. The identification of the acetyl was performed by GC-MS of the silylated acetyl-PBN adduct. Comparison was made against reference adduct from acetyl generated via Fenton reaction and a FAD-NADPH radical generation system acting on acetaldehyde. Formation of acetyl was also observed using pure xanthine oxidase from butter milk. The generation of acetyl by the prostate cytosol was inhibited by allopurinol, oxypurinol, diphenyleneiodonium chloride, folic acid and ellagic acid at low concentrations. Previous and present results suggest that metabolism of ethanol to acetaldehyde and to 1-hydroxyethyl and acetyl radicals could be involved in the deleterious effects of alcohol drinking on prostate epithelial cells. Supported by CONICET and by a grant from the University of San Martín (UNSAM), grant PIB S06/89, Argentina.