Linked Life Data

7923158

Source:http://linkedlifedata.com/resource/pubmed/id/7923158

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1994-11-3
pubmed:abstractText
Tumorigenesis is a multistep genetic process requiring several somatic mutations for neoplastic transformation. These mutations appear to be sequential, random, and independent events. However, we find linked, nonrandom ras mutations occurring during 4-nitroquinoline-1-oxide-induced tumorigenesis months after exposure to the carcinogen had ceased. The carcinogen had been topically applied to the oral cavity of CBA mice for 4 to 16 weeks. Dysplasia developed after 24 weeks, and carcinoma in situ and squamous cell carcinoma developed after 28 weeks. H-ras mutations were detected in 13 of 25 tissue specimens (10 of 14 invasive carcinomas and 2 of 4 carcinoma in situ, 1 of 5 dysplastic tissue, and 0 of 2 normal tissues). Approximately one-half of the tumors had G to A point mutations at codon 12 of the cellular H-ras proto-oncogene on mouse chromosome 7. None had codon 11, 13, or 61 mutations. Loss of heterozygosity occurred in 5 of 14 invasive cancers. Larger invasive squamous cell carcinomas consistently lost the wild-type allele, whereas preneoplastic lesions and small tumors were heterozygous for ras. This suggests a causal relationship between carcinogen treatment, H-ras activation, and initiation of tumorigenesis. The wild-type allele in mouse chromosome 7 is lost with the progression of tumorigenesis long after exposure to the carcinogen. Thus, loss of heterozygosity of the ras gene appears to occur without multiple carcinogen-induced mutations, i.e., as a result of a cascade of events induced by an earlier ras mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
54
pubmed:geneSymbol
H-ras
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5310-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Harvey ras (H-ras) point mutations are induced by 4-nitroquinoline-1-oxide in murine oral squamous epithelia, while squamous cell carcinomas and loss of heterozygosity occur without additional exposure.
pubmed:affiliation
Department of Biochemistry, Henry Vogt Research Institute of the James Graham Brown Cancer Center, University of Louisville, Kentucky.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't