A comparison of the kinetics of low-density lipoprotein oxidation induced by copper or by gamma-rays: Influence of radiation dose-rate and copper concentration

The oxidation of low-density lipoproteins is the first step in the complex process leading to atherosclerosis. The aim of our study was to compare the kinetics of low density lipoprotein oxidation induced by copper ions or by oxygen free radicals generated by Co-60 gamma -rays. The effects of copper concentration and irradiation dose-rate on LDL peroxidation kinetics were also studied. The oxidation of LDL was followed by the measurement of conju gated diene, hydroperoxides, and thiobarbituric acid reactive substance for mation as well as alpha -tocopherol disappearance. In the case of gamma irr adiation, the lag-phase before the onset of lipid peroxidation was inversel y correlated to the radiation dose-rate. The radiation chemical rates (nu) increased with increasing dose-rate. Copper-induced LDL peroxidation follow ed two kinetic patterns: a slow kinetic for copper concentrations between 5 -20 muM, and a fast kinetic for a copper concentration of 40 muM. The conce ntration-dependent oxidation kinetics suggest the existence of a saturable copper binding site on apo-B. When compared with gamma -rays, copper ions a ct as drastic and powerful oxidants only at higher concentrations (greater than or equal to 40 muM).