Linked Life Data

12117783

Source:http://linkedlifedata.com/resource/pubmed/id/12117783

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-7-15
pubmed:abstractText
Evidence suggests that the use of angiotensin-converting enzyme inhibitors potentially reduces the risk of cancer, though the mechanism is unclear. To clarify a potential involvement of angiotensin II (Ang II) signaling in cancer risk, we have examined the effect of Ang II receptor deficiency on azoxymethane (AOM)-induced colon tumorigenesis. Male Ang II type 2 receptor gene-disrupted (AT(2)-null) mice with a 129/Ola and C57BL/6J genetic background, AT(2)-null mice with an SWR/J genetic background, and their corresponding control wild type mice were treated once a week with AOM (10 mg/kg, i.p., 4 consecutive weeks) or saline vehicle. All mice were killed 23-26 weeks after the initial injection of AOM, and tumor burdens were examined. AOM treatment caused the development of colon tumors in all wild type control mice regardless of genetic background (100% tumor prevalence), but only one tumor was present in AT(2)-null mice with a 129/Ola and C57BL/6J genetic background (11.1% tumor prevalence). Although the introduction of the AOMsusceptible SWR/J genetic background induced AOM susceptibility in AT(2) null mice, the tumor multiplicity (6.3) and tumor size (19.8 +/- 3.0 mm(3)) were significantly smaller than those in wild type mice (multiplicity, 12.0 and size, 36.8 +/- 3.2 mm(3)). AOM efficiently downregulated cytochrome P450 2E1 (CYP2E1) in the liver of wild type mice significantly more than in AT(2)-null mice. The levels of DNA methyl adducts formed in wild type mouse colon epithelium by AOM treatment were also significantly higher than in AT(2)-null mice. These results imply that the AT(2) receptor functions to augment AOM-induced downregulation of CYP2E1 expression in the liver, and thus increases AOM-induced tumorigenesis in the colon. The AT(2) receptor function in the liver may be a potential determinant of tumor susceptibility in chemical carcinogen-induced colon tumorigenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1235-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12117783-Animals, pubmed-meshheading:12117783-Azoxymethane, pubmed-meshheading:12117783-Blotting, Western, pubmed-meshheading:12117783-Carcinogens, pubmed-meshheading:12117783-Colon, pubmed-meshheading:12117783-Colonic Neoplasms, pubmed-meshheading:12117783-Crosses, Genetic, pubmed-meshheading:12117783-Cytochrome P-450 CYP2E1, pubmed-meshheading:12117783-DNA Adducts, pubmed-meshheading:12117783-DNA Primers, pubmed-meshheading:12117783-Down-Regulation, pubmed-meshheading:12117783-Endopeptidases, pubmed-meshheading:12117783-Female, pubmed-meshheading:12117783-Genotype, pubmed-meshheading:12117783-Male, pubmed-meshheading:12117783-Mice, pubmed-meshheading:12117783-Mice, Inbred C57BL, pubmed-meshheading:12117783-Mice, Inbred Strains, pubmed-meshheading:12117783-Receptor, Angiotensin, Type 2, pubmed-meshheading:12117783-Receptors, Angiotensin, pubmed-meshheading:12117783-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2002
pubmed:articleTitle
Hemizygous mice for the angiotensin II type 2 receptor gene have attenuated susceptibility to azoxymethane-induced colon tumorigenesis.
pubmed:affiliation
Department of Biochemistry, Vanderbilt University, School of Medicine, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't