SYNERGISTIC DNA-DAMAGING EFFECTS OF MALONDIALDEHYDE CU(II) IN PM2 DNAAND IN HUMAN FIBROBLASTS/

Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In com bination with CuCl2 MDA induced single strand breaks in PM2 DNA wherea s MDA or CuCl2 alone had no effect. Cu(II) oxidized MDA by a radical m echanism under formation of Cu(I). DNA strand break induction was inhi bited by catalase (98%), neocuproine (76%) and DMSO (61%). The synergi stic damaging effect of MDA and Cu(II) was also demonstrated in human fibroblasts measured by alkaline elution. The combination MDA/CuCl2 ca used extensive DNA breakage while neither MDA nor CuCl2 alone induced DNA damage within the cell. Synergistic cytotoxic effects were observe d 18 h after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.