Lycopene entrapped in human albumin protects 2 '-deoxyguanosine against singlet oxygen damage

The generation of electronically excited molecular oxygen O-1(2) has been s hown to occur in several biological systems, such as photooxidation of a va riety of biological compounds and xenobiotics ("photodynamic action") and a lso enzymatic reactions. The high reactivity of O-1(2) With unsaturated com pounds, sulfides and amino groups arises from its electrophilicity and rela tively long lifetime. Thus, biological targets for O-1(2) having the above functional groups include unsaturated fatty acids, proteins, enzymes and DN A. There is interest in the role of nutrition in the prevention and pathoge nesis of cancer. Epidemiological studies in humans have suggested that caro tenoids aid in cancer prevention. Lycopene and oxycarotenoids are present a t significant levels in cells and plasma. Extensively conjugated biomolecul es such as carotenoids act largely on physical quenching of O-1(2) and in m uch lesser extent on chemical reaction. In this study we observed the prote ctive effect of B-carotene and lycopene entrapped in human albumin (HSA) ag ainst the oxidative O-1(2) attack of 2'-deoxyguanosine (dGuo). Photosensiti zation with methylene blue associated with Chelex(R) resine or Polymer-Rose bengal (Sensitox(R)) and thermodecomposition of water-soluble endoperoxide 3,3'-(1,4-naphthylidene) dipropionate were employed to generate O-1(2). Th e detection of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 4-hydrox y-8-oxo-7,8-dihydro-2'-deoxyguanosine (4-OH-8-oxodGuo) were performed using reversed phase HPLC with UV, electrochemical detection and by electrospray ionization mass spectrometry. Results showed a significant decrease in the amount of 8-oxodGuo in the presence of lycopene. The percentages of 4-OH-8 -oxodGuo and 8-oxodGuo measured were 50% and 70% lower than the control, re spectively. These data indicate that carotenoids entrapped in albumin can b e an efficient quencher of O-1(2) and may be of interest in protecting agai nst the deleterious effect of this excited state molecule.