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

Michael Rosemann, Mare Lintrop, Jack Favor, Michael J. Atkinson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 α-particle-emitting radionuclide 227Th, 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.

Original languageEnglish
Pages (from-to)426-434
Number of pages9
JournalRadiation Research
Volume157
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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