Linked Life Data

20041758

Source:http://linkedlifedata.com/resource/pubmed/id/20041758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-31
pubmed:abstractText
This report tests the hypotheses that cancer proneness elevates risk from a high radiation exposure and that the risk response to high doses is qualitatively similar to that from low doses. Groups of about 170 female mice heterozygous for Trp53 (Trp53(+/-)) and their normal female littermates (Trp53(+/+)) were exposed at 7-8 weeks of age to (60)Co gamma-radiation doses of 0, 1, 2, 3 or 4 Gy at a high dose rate (0.5 Gy/min) or 4 Gy at a low dose rate (0.5 mGy/min). In the absence of radiation exposure, Trp53 heterozygosity reduced life span approximately equally for death from either cancer or non-cancer disease. Heterozygosity alone produced a 1.5-fold greater shortening of life span than a 4-Gy acute exposure. Per unit dose, life shortening from cancer or non-cancer disease was the same for normal mice and Trp53 heterozygous animals, indicating that, contrary to previous reports, Trp53 heterozygosity did not confer radiation sensitivity to high doses of gamma rays. In Trp53(+/-) mice with cancer, life shortening from acute doses up to 4 Gy was related to both increased tumor formation and decreased tumor latency. A similar tumor response was observed in normal mice, but only up to 2 Gy, indicating that above 2 Gy, normal Trp53 function protected against tumor initiation, and further life shortening reflected only decreased latency for cancer and non-cancer disease. Dose-rate reduction factors were 1.7-3.0 for both genotypes and all end points. We conclude that Trp53 gene function influences both cancer and non-cancer mortality in unexposed female mice and that Trp53-associated cancer proneness in vivo is not correlated with elevated radiation risk. Increased risk from high acute radiation doses contrasts with the decreased risk seen previously after low doses of radiation in both Trp53 normal and heterozygous female mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1938-5404
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Cancer and non-cancer risks in normal and cancer-prone Trp53 heterozygous mice exposed to high-dose radiation.
pubmed:affiliation
Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario K0J 1J0, Canada.
pubmed:publicationType
Journal Article