Linked Life Data

8895731

Source:http://linkedlifedata.com/resource/pubmed/id/8895731

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1997-1-6
pubmed:abstractText
Peroxisome proliferators, a group of structurally diverse nongenotoxic agents, induce predictable pleiotropic responses in liver, including the development of liver tumors in rats and mice. These agents transcriptionally activate the three genes of the peroxisomal beta oxidation enzyme system by interacting with the peroxisome proliferator-activated receptor(s). It has been proposed that H2O2 generated by the peroxisomal beta oxidation system leads to DNA damage and neoplastic transformation. Consistent with this hypothesis is that cells stably transfected with H2O2-generating peroxisomal fatty acyl-CoA oxidase cDNA, which encodes the first and rate-limiting enzyme of the beta oxidation system, undergo transformation in the presence of a fatty acid substrate. To test whether H2O2 generated by other peroxisomal oxidases can also lead to transformation, a full-length cDNA encoding rat urate oxidase (UOX), which oxidizes uric acid to allantoin and in the process generates H2O2, was introduced into African green monkey kidney cells (CV-1 cells) under the control of constitutively active human peroxisomal fatty acyl-CoA oxidase gene promoter. Five stably transfected CV-1 cell lines expressing recombinant rat UOX were isolated in which the recombinant protein was targeted to peroxisomes and formed crystalloid structures or cores similar to those present in rat liver peroxisomes. Increased levels of H2O2 were found when cells stably expressing UOX were exposed to the substrate uric acid. These five clones, designated A-U1 to A-U5, exhibited anchorage-independent growth, as demonstrated by the formation of transformed colonies in soft agar in proportion to the duration of exposure to uric acid. These transformants exhibited clonal growth under serum-deprived conditions. One of these transformed cell lines, the A-U3 cell line, was evaluated for tumorigenicity by s.c. injection in nude mice. All five mice injected with transformed A-U3 cells developed adenocarcinomas, but no tumors developed in mice injected with control CV-1 cells or cells stably expressing UOX that were not exposed to uric acid. These results provide further evidence indicating that sustained overexpression of a peroxisomal H2O2-generating oxidase causes cell transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4846-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Transformation of epithelial cells stably transfected with H2O2-generating peroxisomal urate oxidase.
pubmed:affiliation
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't