Linked Life Data

19429254

Source:http://linkedlifedata.com/resource/pubmed/id/19429254

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-5-11
pubmed:abstractText
Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is known to be metabolized to organic methylated arsenicals in vivo. As(III) has been reported to have the ability to up-regulate the epidermal growth factor receptor (EGFR)-associated pathway in epithelial cells, including human urothelial cells in vitro. EGFR is a cell-surface receptor belonging to the ErbB family of receptor tyrosine kinases, and the EGFR-associated signaling pathway has been reported to play an important role in carcinogenesis and cancer progression, including in bladder cancer. In this study, we investigated the growth effects of As(III) and an organic trivalent arsenical, dimethylarsinous acid (DMA(III)), and the effects of co-exposure of gefitinib, an EGFR inhibitor, with As(III) to a rat urothelial cell line (MYP3). We also investigated the effects of co-administration of dietary As(III) and gefitinib in vivo. In vitro, concentrations of 1.0microM As(III) or 0.5microM DMA(III) induced cytotoxicity. However, lower concentrations of As(III) treatment had a slight mitogenic growth effect whereas lower concentrations of DMA(III) did not. Gefitinib blocked As(III)-induced cell growth in vitro. In vivo, a high dose of gefitinib alone induced slight urothelial cytotoxicity, and did not reduce cytotoxicity and regenerative cell proliferation when co-administered with As(III). The majority of arsenic metabolites present in the urine of As(III)-treated rats were organic arsenicals, mainly dimethylarsinic acid (DMA(V)). As(III) was also present, and its concentration was higher than the concentration required to produce cytotoxicity in vitro. These data suggest that an EGFR inhibitor has the ability to block As(III)-induced cell proliferation in vitro but not in vivo in a short-term study.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
124-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effects of an epidermal growth factor receptor inhibitor on arsenic associated toxicity in the rat bladder epithelium.
pubmed:affiliation
Department of Pathology and Microbiology and the Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
pubmed:publicationType
Journal Article