Synergistic DNA damaging effects of malondialdehyde/Cu(II) in PM2 DNA and in human fibroblasts.
Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In combination with CuCl2 MDA induced single strand breaks in PM2 DNA whereas MDA or CuCl2 alone had no effect. Cu(II) oxidized MDA by a radical mechanism under formation of Cu(I). DNA strand break induction was inhibited by catalase (98%), neocuproine (76%) and DMSO (61%). The synergistic damaging effect of MDA and Cu(II) was also demonstrated in human fibroblasts measured by alkaline elution. The combination MDA/CuCl2 caused extensive DNA breakage while neither MDA nor CuCl2 alone induced DNA damage within the cell. Synergistic cytotoxic effects were observed 18 h after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h.
Vöhringer
M L
ML
Carl-von-Ossietzky Universität Oldenburg, ICBM and FB7, Germany.
Becker
T W
TW
Krieger
G
G
Jacobi
H
H
Witte
I
I
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001435:Bacteriophages / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000032:analysis / Q000633:toxicity*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008315:Malondialdehyde / Q000633:toxicity*; D010618:Phenanthrolines / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D002614:Chelating Agents; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D010618:Phenanthrolines; D008315:Malondialdehyde; D003300:Copper; C002701:neocuproine; C028419:cuprous chloride; C029892:cupric chloride; D004121:Dimethyl Sulfoxide