Site-specific DNA damage caused by lipid peroxidation products.
DNA damage induced by autoxidized lipids was investigated using covalently closed circular (supercoiled) DNA and DNA fragments of defined sequence. DNA-strand-breaking substances accumulated during autoxidation of methyl linolenate, and strand breakage was measured with samples taken at different times. The DNA-strand-breaking activity reached its maximum a little after the peak value of peroxide and decreased upon further autoxidation. The peak of the DNA-strand-breaking activity did not always coincide with the peak of thiobarbituric acid reactants or of conjugated diene, either. The DNA-strand-breaking reaction was dependent on metal ions and was inhibited by potassium iodide and tiron and partially by catalase, suggesting the involvement of radical species and/or oxygen radicals. No direct cleavage of singly end-labeled 100-200 basepair DNA fragments by autoxidized methyl linolenate and cupric ion was detected under the conditions used. Cleavage occurred during subsequent heating in piperidine after the reaction. The alkali-labile damage was preferentially induced at pyrimidine residues, especially in dinucleotide sequences of pyrimidine-guanine (5'----3'), which was determined by sequencing.
Ueda
K
K
Kobayashi
S
S
Morita
J
J
Komano
T
T
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D010584:Bacteriophage phi X 174 / Q000235:genetics; D001435:Bacteriophages / Q000235:genetics; D001483:Base Sequence; D002374:Catalase / Q000494:pharmacology; D002412:Cations; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D004278:DNA, Superhelical; D004279:DNA, Viral; D005609:Free Radicals; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008670:Metals / Q000494:pharmacology; D010084:Oxidation-Reduction; D011193:Potassium Iodide / Q000494:pharmacology
D002412:Cations; D004278:DNA, Superhelical; D004279:DNA, Viral; D005609:Free Radicals; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008670:Metals; D011193:Potassium Iodide; C005575:methyl linoleate; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D004247:DNA; D002374:Catalase