An in vitro model for studying oxidative damage and protective substances in human cells

By Monti, D. - Barozzi, D. - Buttafoco, P. - Troiano, L. - Tropea, F. - Cossarizza, A. - Grassilli, E. - Pelioni, M.C. - Marini, M. - Tiozzo, R.

An in vitro experimental system comprising human peripheral blood lymphocytes or rat splenocytes exposed to oxygen free radicals (OFR) generated extracellularly by a classic enzymatic system, i.e. xanthine oxidase (XOD) plus hypoxanthine (HYP), is proposed as a model for the study of OFR-induced damage, for investigating the mechanisms responsible for cell injury and for identifying possible protective substances. We show that rat splenocytes are much more sensitive than human lymphocytes to oxidative stress. The protective effects exerted on OFR-exposed human lymphocytes by inhibitors of poly(ADP-ribosyl)polymerase (ADPRP), such as 3-aminobenzamide, 3-methoxybenzamide and nicotinamide, suggest that the activation of ADPRP is a critical step in the metabolic pathways which mediate the toxic effect of OFR in human cells.