Hypochlorous acid-induced base modifications in isolated calf thymus DNA.
Exposure of calf thymus DNA to hypochlorous acid/hypochlorite leads to extensive DNA base modification. Large concentration-dependent increases in pyrimidine oxidation products [thymine glycol (cis/trans), 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxyhydantoin] but not purine oxidation products (8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guanine, FAPy adenine) were observed at pH 7.4. In addition, large increases in 5-chlorouracil (probably formed from 5-chlorocytosine during sample preparation), a novel chlorinated base, were observed. Addition of HOCl to DNA already damaged by .OH generated by a mixture of ascorbate, copper(II) chloride, and hydrogen peroxide showed that hypochlorous acid led to a loss of 8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guanine, FAPy adenine, and 5-hydroxycytosine in a concentration- and pH-dependent manner. Nevertheless, time course studies suggested that the formation of purine oxidation products in isolated DNA by hypochlorous acid was not a major oxidation pathway. If this pattern of damage, especially the production of 5-chlorocytosine, is unique to hypochlorous acid, it might act as a "fingerprint" of damage to DNA by HOCl.
Whiteman
M
M
International Antioxidant Research Centre, University of London, Kings College, England. MATT.WHITEMAN@kcl.ac.uk
Jenner
A
A
Halliwell
B
B
D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000737:chemistry*; D007700:Kinetics; D008670:Metals / Q000737:chemistry; D010084:Oxidation-Reduction; D013950:Thymus Gland / Q000737:chemistry*; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry
D008670:Metals; D014498:Uracil; D006997:Hypochlorous Acid; C010889:5-chlorouracil; D004247:DNA