Comparison of oxidative damage of DNA and lipids in normal and tumor rat hepatocyte cultures treated with ferric nitrilotriacetate.
Oxidative damage of DNA and lipids in normal primary rat hepatocyte cultures and in hepatoma Fao cell-line was induced by ferric nitrilotriacetate (Fe-NTA). DNA oxidation was evidenced by measuring the mutagenic oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxodG). An increase in 8-oxodG production was induced by Fe-NTA in the two different cell cultures. Moreover, this increase was more important in hepatocytes than in Fao cells. In addition, the extent of lipid peroxidation was higher in normal hepatocytes than in Fao cells. These observations demonstrated a higher resistance of tumor cells than normal hepatocytes to oxidative stress. Since DNA lesions induced by oxidative stress are now recognized as being involved in the mutagenesis process and since normal hepatocytes appeared particularly sensitive to iron-induced oxidative damage, a high level of iron should be considered as a potent toxic factor involved in normal cell degeneration. This findings might partly explain the propensity of hepatic iron-overload diseases for cancerous evolution.
Morel
I
I
Laboratoire de Biologie Cellulaire et Végétale, INSERM U456, UFR des Sciences Pharmaceutiques, 2 av. du Pr. Léon Bernard, 35043 Rennes, France. isabelle.morel@univ-rennesl.fr
Hamon-Bouer
C
C
Abalea
V
V
Cillard
P
P
Cillard
J
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D005290:Ferric Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate