Hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids induce sister chromatid exchanges in cultured mammalian cells.
Oxygen radical-induced genetic damage may be mediated by products of lipid peroxidation, in particular, arachidonic acid. Several isomeric hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids (HETEs and HPETEs), intermediates of arachidonic acid metabolism, were evaluated for their ability to cause sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Both HETEs and HPETEs induced SCEs in a dose-dependent fashion at concentrations of 5, 10, and 20 microM. At each concentration, HETEs were more effective in producing SCEs than the corresponding HPETEs. Each of the isomeric forms used were equally effective in producing genetic damage. Antioxidants (superoxide dismutase, catalase and mannitol) were protective suggesting an intermediate role for the hydroxyl radical. Iron chelation by desferrioxamine suppressed SCE induction by 45% and an additional 33% inhibition was observed upon the addition of the calcium chelator EGTA.
Weitberg
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AB
Division of Hematology/Oncology, Roger Williams Cancer Center, Providence, Rhode Island.
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003676:Deferoxamine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005609:Free Radicals; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D015289:Leukotrienes / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000494:pharmacology
D005609:Free Radicals; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D008353:Mannitol; D004533:Egtazic Acid; C021201:12-HPETE; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine