Linked Life Data

8118927

Source:http://linkedlifedata.com/resource/pubmed/id/8118927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-4-7
pubmed:abstractText
The genotoxic/mutagenic mechanism(s) of action of fecapentaene-12 (fec-12) is complex but there is evidence to suggest that the generation of active oxygen species (AOS) may be involved. This has been assessed by measuring the formation of 8-hydroxydeoxyguanosine (8-OHdG) in isolated DNA and HeLa cells exposed in vitro to fec-12. The possibility that fec-12 may form AOS via peroxidative 'activation' by prostaglandin H synthase (PHS) has been investigated by measuring 8-OHdG in HeLa cells exposed to fec-12 in the absence or presence of PHS inhibitors. The role of iron as a catalyst in this pathway has also been investigated. A 4-fold increase in the level of 8-OHdG in isolated DNA was seen after exposure to fec-12 (1 mM) alone. This increase was enhanced synergistically by ferrous iron. Fec-12 exposure of HeLa cells at 50 and 100 microM induced 2- and 3-fold increases (P < 0.001) respectively in the level of 8-OHdG in cellular DNA. No increase was seen at 10 microM fec-12. The PHS inhibitors indomethacin and acetylsalicylate blocked the formation of 8-OHdG induced by fec-12 (50 microM) but did not inhibit the formation of 8-OHdG in these cells after exposure to H2O2 and Fe2+. Addition of the iron chelating agent o-phenanthroline to cells prior to fec-12 exposure blocked the increase in 8-OHdG induced by fec-12 (50 microM). Addition of the radical scavenging agent DMSO (10%) to cells prior to fec-12 exposure reduced the level of 8-OHdG to within 10% of control. Specific inhibition of fec-12 induced 8-OHdG formation in HeLa cells by PHS inhibitors suggests that this enzyme may be involved in 'activating' fec-12 to form AOS in cells. Inhibition of fec-12 induced 8-OHdG formation in cells by o-phenanthroline suggests a role for intracellular iron as a catalyst in this process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
449-53
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Induction of 8-hydroxydeoxyguanosine in isolated DNA and HeLa cells exposed to fecapentaene-12: evidence for the involvement of prostaglandin H synthase and iron.
pubmed:affiliation
Centre for Mechanisms of Human Toxicity, Leicester, UK.
pubmed:publicationType
Journal Article