Linked Life Data

18824180

Source:http://linkedlifedata.com/resource/pubmed/id/18824180

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2008-10-30
pubmed:abstractText
Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6x10(6) tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P=0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log2 of nuclear mutant cluster size plotted against log2 of the number of clusters of a given cluster size displayed a slope of approximately 1.1 over a range of cluster sizes from approximately 2(6) to 2(15) mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
646
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-40
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: absence of detectable effects of age, gender or smoking status.
pubmed:affiliation
Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139, United States.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural