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Physical, heritable and age-related factors as modifiers of radiation cancer risk in patched heterozygous mice.

TitlePhysical, heritable and age-related factors as modifiers of radiation cancer risk in patched heterozygous mice.
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2009
AuthorsPazzaglia, Simonetta, Pasquali Emanuela, Tanori Mirella, Mancuso Mariateresa, Leonardi Simona, Di Majo Vincenzo, Rebessi Simonetta, and Saran Anna
JournalInt J Radiat Oncol Biol Phys
Volume73
Issue4
Pagination1203-10
Date Published2009 Mar 15
ISSN1879355X
KeywordsAge Factors, Animals, Animals, Newborn, Apoptosis, Cerebellar Neoplasms, Dose-Response Relationship, Radiation, heterozygote, Loss of Heterozygosity, medulloblastoma, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Neoplasms, Radiation-Induced, patched receptors, Patched-1 Receptor, Precancerous Conditions, Receptors, Cell Surface, Stem cells, Whole-Body Irradiation
Abstract

PURPOSE: To address the tumorigenic potential of exposure to low/intermediate doses of ionizing radiation and to identify biological factors influencing tumor response in a mouse model highly susceptible to radiogenic cancer.

METHODS AND MATERIALS: Newborn Ptc1 heterozygous mice were exposed to X-ray doses of 100, 250, and 500 mGy, and tumor development was monitored for their lifetime. Additional groups were irradiated with the same doses and sacrificed at fixed times for determination of short-term endpoints, such as apoptosis and early preneoplastic lesions in cerebellum. Finally, groups of Ptc1 heterozygous mice were bred on the C57BL/6 background to study the influence of common variant genes on radiation response.

RESULTS: We have identified a significant effect of low-intermediate doses of radiation (250 and 500 mGy) in shortening mean survival and inducing early and more progressed stages of tumor development in the cerebellum of Ptc1(+/-) mice. In addition, we show that age at exposure and heritable factors are potent modifiers of radiation-related cancer risk.

CONCLUSIONS: The Ptc1 knockout mouse model offers a highly sensitive system that may potentially help to improve understanding and quantification of risk at low doses, such as doses experienced in occupational and medical exposures, and clarify the complex interactions between genetic and environmental factors underlying cancer susceptibility.

DOI10.1016/j.ijrobp.2008.10.068
Alternate JournalInt. J. Radiat. Oncol. Biol. Phys.
Citation Key5071
PubMed ID19201105