Lipid peroxidation and cytotoxicity of Ehrlich ascites tumor cells by ferric nitrilotriacetate.
Ferric nitrilotriacetate, which causes in vivo organ injury, induced lipid peroxidation and cell death in Ehrlich ascites tumor cells in vitro. The process was inhibited by butylated hydroxyanisole and enhanced by vitamin C and linolenic acid, indicating a close relationship between cytotoxicity and the lipid peroxidizing ability of Fe3+ NTA. The cytotoxicity was suppressed by glucose and a temperature below 20 degrees C. Lipid peroxidation of Fe3+ NTA-treated cells was greater at 0 degree C than at 37 degrees C, contrary to results with Fe3+ NTA-treated plasma membranes of Ehrlich ascites tumor cell. These results suggested that metabolism and membrane fluidity are important factors in the expression of the Fe3+ NTA-induced cytotoxicity. H2O2 showed a lower cytotoxicity than did Fe3+ NTA but a greater lipid peroxidizing ability. H2O2 appeared to damage the cells less, and was quenched rapidly by cellular metabolism unlike Fe3+ NTA. In transferrin-free medium, Ehrlich ascites tumor cell readily incorporated Fe3+ NTA, and iron uptake was greater than NTA-uptake in Fe3+ NTA-treated cells, suggesting that Ehrlich ascites tumor cell incorporated iron from Fe3+NTA and metabolized it into an inert form such as ferritin.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D008042:Linolenic Acids / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D013696:Temperature; D017962:alpha-Linolenic Acid
D005290:Ferric Compounds; D008042:Linolenic Acids; D008054:Lipid Peroxides; D017962:alpha-Linolenic Acid; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007501:Iron; D005947:Glucose; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate