Evidence for mitochondrial DNA damage by lipid peroxidation.
When mitochondria of rat liver were incubated in an in vitro system containing NADPH and ferrous chloride, marked lipid peroxidation occurred, as evidenced by the evolution of malonic dialdehyde. DNA isolated from these peroxidized mitochondrial preparations had completely different electrophoretic mobility than DNA isolated from mitochondria protected from peroxidation. Scavengers of superoxide anion, hydrogen peroxide and hydroxyl radicals offered no protection against either lipid peroxidation or DNA damage. However, alpha-tocopherol protected against both lipid peroxidation and damage to the mitochondrial genome. These results support the hypothesis that lipid peroxidation can mediate DNA damage.
Hruszkewycz
A M
AM
Department of Pathology, George Washington University Medical Center, Washington, D.C. 20037.
D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005296:Ferrous Compounds / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides; D017665:Hydroxyl Radical; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology
D004272:DNA, Mitochondrial; D005296:Ferrous Compounds; D006878:Hydroxides; D008054:Lipid Peroxides; D014810:Vitamin E; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D009249:NADP; D006861:Hydrogen Peroxide; C029451:ferrous chloride