Linked Life Data

11316574

Source:http://linkedlifedata.com/resource/pubmed/id/11316574

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-4-24
pubmed:abstractText
We report here the relative roles of metals and selected reactive oxygen species in DNA damage by the genotoxic benzene metabolite 1,2,4-benzenetriol, and the interactions of antioxidants in affording protection. 1,2,4-Benzenetriol induces scission in supercoiled phage DNA in neutral aqueous solution with an effective dose (ED(50)) of 6.7 microM for 50% cleavage of 2.05 microg/ml supercoiled PM2 DNA. In decreasing order of effectiveness: catalase (20 U/ml), formate (25 mM), superoxide dismutase (20 U/ml), and mannitol (50 mM) protected, from 85 to 28%. Evidently, H(2)O(2) is the dominant active species, with O(2)(*)(-) and *OH playing subordinate roles. Desferrioxamine or EDTA inhibited DNA breakage by 81-85%, despite accelerating 1,2,4-benzenetriol autoxidation. Consistent with this suggestion of a crucial role for metals, addition of cupric, cuprous, ferric, or ferrous ions enhanced DNA breakage, with copper being more active than iron. Combinations of scavengers protected more effectively than any single scavenger alone, with implications for antioxidants acting in concert in living cells. Synergistic combinations were superoxide dismutase with *OH scavengers, superoxide dismutase with desferrioxamine, and catalase with desferrioxamine. Antagonistic (preemptive) combinations were catalase with superoxide dismutase, desferrioxamine with *OH scavengers, and catalase with *OH scavengers. The most striking aspect of synergism was the extent to which metal chelation (desferrioxamine) acted synergistically with either catalase or superoxide dismutase to provide virtually complete protection. Concluding, 1,2,4-benzenetriol-induced DNA damage occurs mainly by site-specific, Fenton-type mechanisms, involving synergism between several reactive intermediates. Multiple antioxidant actions are needed for effective protection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Catalase, http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Bacterial, http://linkedlifedata.com/resource/pubmed/chemical/Formic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Hydroquinones, http://linkedlifedata.com/resource/pubmed/chemical/Mannitol, http://linkedlifedata.com/resource/pubmed/chemical/Metals, http://linkedlifedata.com/resource/pubmed/chemical/Mutagens, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase, http://linkedlifedata.com/resource/pubmed/chemical/formic acid, http://linkedlifedata.com/resource/pubmed/chemical/hydroxyhydroquinone
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
943-56
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
DNA breakage induced by 1,2,4-benzenetriol: relative contributions of oxygen-derived active species and transition metal ions.
pubmed:affiliation
Bioenergetics Research Laboratory, Faculty of Applied Sciences, Simon Fraser University, Burnaby, BC, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't