Is lipid peroxidation associated with DNA damage?
Specific binding to DNA of lipid peroxidation products was studied in rat hepatocytes labeled with [14C(U)]arachidonic acid after incubation at 37 degrees C either in the absence or in the presence of 200 microM FeSO4. The results obtained show that: (1) production of malondialdehyde-like thiobarbituric-reactive substances occurred in the absence of FeSO4 and was increased, albeit quite variably, by exposure to this pro-oxidant; (2) a low but appreciable binding of radioactivity to DNA and protein was constantly detected in 5 independent experiments; (3) there was no quantitative correlation between malondialdehyde formation and the amount of DNA-bound and protein-bound radioactivity, and any meaningful evidence of a GSH-depletion effect was absent. Taking into account the possible biosynthetic incorporation of radioactivity into DNA, the results of this study must be interpreted with caution, and solely as indicating that in the intact cell the covalent binding to DNA of reactive species generated by lipid peroxidation, if it occurs, should be minimal, corresponding in our experimental conditions approximately to 0.01 mumole of radioactive arachidonic acid per mole nucleotides.
Institute of Pharmacology, University of Genoa, Italy.
G
G
Brambilla
A
A
Martelli
U M
UM
Marinari
D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification; D004249:DNA Damage; D005296:Ferrous Compounds / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D005296:Ferrous Compounds; D011506:Proteins; C020748:ferrous sulfate; D008315:Malondialdehyde; D004247:DNA