Apr 19, 1985

Site-specific DNA damage caused by lipid peroxidation products

Biochimica Et Biophysica Acta
K UedaT Komano

Abstract

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.

  • References12
  • Citations46

References

  • References12
  • Citations46

Mentioned in this Paper

methyl linoleate, 1-(14)C-labeled, (Z,Z)-isomer
DNA, Viral
Bacteriophages
Free Radicals
Lipid Peroxides
Metals
Linoleic Acids
Cations
Tiron
DNA, Superhelical

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