ABSTRACT

Hot (100 °C) and cold (20 °C) water extracts of the fruit bodies of selected mushroom species have been tested for their ability to prevent H₂O₂-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis ("Comet") assay. Highest genoprotection was observed with cold water and hot water extracts of Agaricus bisporus (J.Lge) Imbach and Ganoderma lucidum (W. Curt.:Fr.) Lloyd fruit bodies, respectively. The genoprotective effect of A. bisporus is associated with a heat-labile protein that has been purified following salt fractionation, combined with ion-exchange, hydrophobic interaction, and adsorption chromatography. Based on catalytic and electrophoretic properties and enzyme inhibition studies, the protein was identified as tyrosinase. The genoprotective effect of the protein is dependent upon the enzyme-catalyzed conversion of tyrosine to L-DOPA and subsequent conversion of this metabolite to tyrosinase-generated L-DOPA oxidation products such as dopaquinone. We propose that these oxidation products trigger cellular processes that upregulate the overall antioxidant status of the cell and could be incorporated into preventive strategies and treatments of pathological conditions associated with elevated oxidative DNA damage and other manifestations of increased oxidative stress.