Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-9-4
pubmed:abstractText
Severe combined immunodeficiency (Scid) mice have defects in V(D)J recombination and DNA double-strand breaks repair caused by an inherited genetic defect in the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Scid mice are highly susceptible to development of T-cell lymphomas, and because of the nature of its association with DNA repair and recombination, DNA-PKcs is considered to belong to the caretaker class of tumor suppressor genes. In the present study, the susceptibility of Scid mice to colon carcinogenesis due to administration of azoxymethane (AOM) was investigated. Significantly higher susceptibility in terms of induction of both aberrant crypt foci (ACFs), putative pre-cancerous lesions of the colon and colon cancers was observed as compared with the isogenic strain, C.B-17 mice. The incidences of colon tumors, either adenomas or adenocarcinomas, in Scid and C.B-17 mice after administration of AOM (10 mg/kg body weight/week) for 6 weeks were 87% (26 of 30) and 50% (15 of 30), respectively, by experimental week 22 (P < 0.01). The multiplicity of colon tumors in Scid mice was also significantly higher than in C.B-17 mice, being 2.2 +/- 1.5 and 0.9 +/- 1.2, respectively (P < 0.001). The present study clearly demonstrated high susceptibility of Scid mice to colon carcinogenesis, which might be attributable to disruption of the caretaker role of DNA-PK in colonic epithelial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1551-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11532879-Adenocarcinoma, pubmed-meshheading:11532879-Animals, pubmed-meshheading:11532879-Azoxymethane, pubmed-meshheading:11532879-Carcinogens, pubmed-meshheading:11532879-Cocarcinogenesis, pubmed-meshheading:11532879-Colonic Neoplasms, pubmed-meshheading:11532879-Cytoskeletal Proteins, pubmed-meshheading:11532879-DNA-Activated Protein Kinase, pubmed-meshheading:11532879-DNA-Binding Proteins, pubmed-meshheading:11532879-Female, pubmed-meshheading:11532879-Genetic Predisposition to Disease, pubmed-meshheading:11532879-Mice, pubmed-meshheading:11532879-Mice, SCID, pubmed-meshheading:11532879-Mutation, pubmed-meshheading:11532879-Precancerous Conditions, pubmed-meshheading:11532879-Protein-Serine-Threonine Kinases, pubmed-meshheading:11532879-Trans-Activators, pubmed-meshheading:11532879-beta Catenin
pubmed:year
2001
pubmed:articleTitle
High susceptibility of Scid mice to colon carcinogenesis induced by azoxymethane indicates a possible caretaker role for DNA-dependent protein kinase.
pubmed:affiliation
Biochemistry Division and Cancer Prevention Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't