title: Evidence that lipid peroxidation products bind to DNA in liver cells.
abstract: 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.
mesh_terms: 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
chemical_list: 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