Evidence that lipid peroxidation products bind to DNA in liver cells.
Three lines of evidence are presented indicating the association of lipid peroxidation products with DNA in liver cells, labeled with [3H]arachidonic acid, in the presence of Fe(2+)-DTPA: (1) the nuclear DNA isolated from treated cells had higher radioactivity, compared to controls and the radioactivity increased with longer incubation times, (2) lipid-DNA adducts with a characteristic fluorescence spectrum were formed during the incubation with Fe(2+)-DTPA; (3) the association of peroxidation products with DNA could be inhibited by vitamin E and BHT. Compared with control DNA, purified lipid-DNA adducts showed a decrease of hyperchromicity and melting point, and partial resistance to hydrolysis by DNase I. On the other hand, the repair test shows that the lipid-DNA adducts in cells were not repaired by 4 h after removal of Fe(2+)-DTPA. A decrease in cell viability and in the activity of O6-alkylguanine acceptor protein was also observed with increasing incubation time. These data suggest that the lipid-DNA association, an oxidative DNA damage, occurs in cells treated by Fe(2+)-DTPA and could result in cytotoxicity if not repaired.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002467:Cell Nucleus / Q000737:chemistry; D002470:Cell Survival; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D014316:Tritium; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005296:Ferrous Compounds; D008054:Lipid Peroxides; D014316:Tritium; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D016718:Arachidonic Acid; D006147:Guanine; D004369:Pentetic Acid; D004247:DNA; C008449:O-(6)-methylguanine; D003850:Deoxyribonuclease I