Journal Article

Outbred CD-1 mice carry the susceptibility allele at the pulmonary adenoma susceptibility 1 (<i>Pas1</i>) locus

Giacomo Manenti, Federica Galbiati, Sara Noci and Tommaso A. Dragani

in Carcinogenesis

Volume 24, issue 6, pages 1143-1148
Published in print June 2003 | ISSN: 0143-3334
Published online June 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg065
Outbred CD-1 mice carry the susceptibility allele at the pulmonary adenoma susceptibility 1 (Pas1) locus

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CD-1 is the outbred mouse line most often used in toxicology and carcinogenicity bioassays. A literature survey revealed a relatively high (21.8%) incidence of spontaneous lung tumors in these mice, and a susceptibility to lung tumorigenesis induced by vinyl chloride, styrene or benzene inhalation that is not seen in B6C3F1 or C57BL/6 mice, or in rats and hamsters. As the pulmonary adenoma susceptibility 1 (Pas1) locus is the major determinant of genetic susceptibility to lung tumorigenesis in mice, we analyzed CD-1 mice for genetic polymorphisms of the Kras2 and Pthlh genes, which are tightly linked with the Pas1 locus. From 95 to 98% of CD-1 mice carried the susceptibility allele at the Pas1 locus either at homozygosity or heterozygosity, providing a molecular genetic explanation for the high susceptibility of CD-1 mice to spontaneous and chemically induced lung tumorigenesis. These results may have implications for the risk assessment of chemicals in humans using experimental animals that display strain-specific lung tumorigenicity.

Keywords: Pas1, pulmonary adenoma susceptibility 1; VC, vinyl chloride

Journal Article.  4296 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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