Linked Life Data

18375078

Source:http://linkedlifedata.com/resource/pubmed/id/18375078

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-4-14
pubmed:abstractText
7-Hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3',2':4,5]imidazo[1,2-a]pyrimidin-5-ium chloride (PhIP-M1) is a newly identified intestinal microbial metabolite from the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Although the mutagenic potential of the endogenous N-hydroxy PhIP derivate has been reported, the risks associated with PhIP-M1 have not yet been explored. In this work, the cytotoxic and genotoxic effects originating from PhIP-M1 were assessed in the epithelial intestinal Caco-2 cell line. PhIP-M1 significantly decreased in a time- and dose-dependent manner mitochondrial dehydrogenase activity and protein synthesis, with IC50 values of, respectively, 180+/-39.4 and 173+/-20.3 microM after 24h, and 33.8+/-3.5 and 37.3+/-10.9 microM after 72 h. Apoptosis within the concentration ranges of cytotoxicity was confirmed by morphological examination, DAPI nuclear staining and annexin V staining. PhIP-M1 provoked cell cycle arrest, characterized by a significant increase in the number of nucleoids in the G2/M phase. A dose-dependent increase in DNA damage, as quantified by the alkaline comet assay, was observed after 3h in the 50-200 microM range. Because these PhIP-M1-induced genomic and cellular events may contribute to the carcinogenicity of PhIP, the potency of the colon microbiota to bioactivate PhIP must be included in future risk assessments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-9
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The microbial PhIP metabolite 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3',2':4,5]imidazo[1,2-a]pyrimidin-5-ium chloride (PhIP-M1) induces DNA damage, apoptosis and cell cycle arrest towards Caco-2 cells.
pubmed:affiliation
Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University-UGent, Coupure Links 653, B-9000 Ghent, Belgium. Lynn.Vanhaecke@ugent.be
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't