Linked Life Data

15261988

Source:http://linkedlifedata.com/resource/pubmed/id/15261988

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-7-20
pubmed:abstractText
The chlorohydroxyfuranones (CHFs) MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone], MCA [3,4-dichloro-5-hydroxy-2(5H)-furanone], CMCF [3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone], and MCF [3-chloro-4-methyl-5-hydroxy-2(5H)-furanone] are genotoxic disinfection by-products of drinking water chlorination. MX, MCA, and MCF also promote foci formation in the two-stage cell transformation assay. The cellular mechanisms underlying this apparent promotional effect are not known. In the present study, the effects of MX, MCA, CMCF, and MCF on gap junctional intercellular communication (GJIC) were measured in BALB/c 3T3 cells using the scrape loading dye technique. The effect of MX on apoptosis in the same cell line was explored by assaying caspase-3-like protease activity. All the four CHFs inhibited GJIC after 30 min exposure in a dose-dependent fashion but there was a marked difference in the ranges of their active concentrations. MX was almost as potent an inhibitor of GJIC (inhibition at nanomolar concentrations) as 12-O-tetradecanoylphorbol-13-acetate (TPA) (positive control), while MCA was 10 times weaker, CMCF 10,000 times weaker, and MCF 20,000 times weaker than MX. After prolonged exposure periods (up to 6 h), GJIC recovered somewhat upon MX and MCA exposures, the inhibition of GJIC by MCF remained constant but CMCF showed an irreversible increasing inhibitory effect. MX caused apoptosis as a "window" effect at concentrations 2000-4000-fold higher than those needed to inhibit GJIC. The results indicate that MX is a potent inhibitor of GJIC in BALB/c 3T3 cells and this inhibition might be one mechanism by which MX can promote malignant foci formation. MCA also has a specific potential to inhibit GJIC whereas MCF and CMCF affected GJIC at concentrations, similar to those evoking genotoxicity in vitro.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
439-49
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Potent inhibition of gap junctional intercellular communication by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in BALB/c 3T3 cells.
pubmed:affiliation
National Public Health Institute, Laboratory of Toxicology, P.O. Box 95, Kuopio FIN-70701, Finland. pasi.hakulinen@ktl.fi
pubmed:publicationType
Journal Article