Suppression of free radical-induced DNA strand breaks by linoleic acid and low density lipoprotein in vitro.
The results of the present study have shown that unoxidized linoleic acid (LA) and low density lipoprotein (LDL) suppressed free radical-induced supercoiled plasmid DNA strand breaks. Unoxidized LA suppressed DNA strand breaks induced by free radicals generated from hydrogen peroxide/Fe(II) ion, 2'-azobis(2-amidinopropane)hydrochloride (AAPH), and 4-(hydroxymethyl)benzene diazonium salt. Thiobarbituric acid reactive substances (TBARS) of LA were increased on treatment with the radical generators. The intensities of the electron spin resonance (ESR) signals of the spin adducts of the radicals were reduced by unoxidized LA. Although LA hydroperoxide caused DNA strand breaks as has already been shown, its strand breaking activity was observed only at the higher concentrations. Unoxidized LDL inhibited ascorbic acid/Cu(II) ion-, ascorbic acid/Fe(II) ion-, peroxynitrite- and AAPH-induced DNA strand breaks. The TBARS of LDL were increased by treatment with the agents. LDL oxidized with Cu(II) ion did not cause DNA strand breaks. The results indicate that the potency of the free radicals to cause DNA strand breaks was attenuated by the fatty acid and the lipoprotein through lipid peroxidation.
Hiramoto
Kazuyuki
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
Yasuhara
Yoshinobu
Y
Sako
Ken-ichi
K
Aoki
Kazuhiro
K
Kikugawa
Kiyomi
K
D004249:DNA Damage / Q000187:drug effects*; D005609:Free Radicals / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*
D005609:Free Radicals; D008077:Lipoproteins, LDL; D019787:Linoleic Acid