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Rosemann, M. ; Lintrop, M. ; Favor, J. ; Atkinson, M.J.

Bone tumorigenesis induced by alpha-particle radiation: Mapping of genetic loci influencing predisposition in mice.

Radiat. Res. 157, 426-434 (2002)
Publ. Version/Full Text DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The present study was carried out to determine the extent to which genetic factors modify the incidence of radiation-induced bone tumorigenesis in mice, and to map putative susceptibility genes. We conducted a genome-wide linkage analysis in a cohort of 47 interstrain backcrossed mice. After the mice were injected with the bone-seeking alpha-particle-emitting radionuclide Th-227, 21 of the mice developed osteosarcomas. Two loci, one on chromosome 7 close to D7Mit145 and a second on chromosome 14 (D14Mit125), exhibited suggestive linkage to osteosarcoma predisposition, with LOD scores of 1.37 and 1.05, respectively. The LOD score increased considerably when interaction between these two loci was taken into account (LOD = 3.48). Nine of 12 mice inheriting a susceptibility allele at both loci developed osteosarcomas after 227Th injection, compared to only four osteosarcomas in 18 animals that did not inherit either of the susceptibility alleles. Variance component analysis revealed that these genetic factors determine approximately one-fifth of the total incidence of osteosarcomas. This study demonstrates the presence of a genetic component that modulates predisposition to radiation-induced osteosarcoma.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords TUMOR-SUPPRESSOR GENE; RETINOBLASTOMA GENE; COMPLEX TRAITS; OSTEO-SARCOMA; LUNG-CANCER; OSTEOSARCOMA; MOUSE; P53; MUTATIONS; CHILDREN
ISSN (print) / ISBN 0033-7587
e-ISSN 1938-5404
Journal Radiation Research
Quellenangaben Volume: 157, Issue: , Pages: 426-434 Article Number: , Supplement: ,
Publisher Radiation Research Society
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Institute of Developmental Genetics (IDG)
Institute of Human Genetics (IHG)