Hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids induce DNA strand breaks in human lymphocytes.
Oxygen radical-induced genetic damage may be mediated by products of lipid peroxidation, in particular, arachidonic acid. Hydroxy- and hydroperoxyeicosatetraenoic acids (HETEs and HPETEs) are intermediates in the metabolism of arachidonic acid to the leukotrienes. Several isomeric hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids were evaluated for their ability to cause DNA single-strand breaks in human lymphocytes. Both HETEs and HPETEs induced strand breaks in a dose-dependent fashion at concentrations of 5, 10 and 20 microM. At each concentration, HETEs were more effective in producing breakage than the corresponding HPETEs. Each of the isomeric forms used were equally effective in producing strand breaks. Antioxidants (superoxide dismutase, catalase and mannitol) were protective. Iron chelation by desferrioxamine suppressed strand breakage by 45% and an additional 33% inhibition was observed upon the addition of the calcium chelator EGTA.
Weitberg
A B
AB
Division of Hematology/Oncology, Roger Williams Cancer Center, Providence, RI.
Corvese
D
D
D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D015289:Leukotrienes / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*
D000975:Antioxidants; D004277:DNA, Single-Stranded; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D004533:Egtazic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; D004247:DNA; D003676:Deferoxamine