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Carcinogenesis Advance Access published online on April 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg065
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CARCINOGENESIS

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

Giacomo Manenti 1, Federica Galbiati 1, Sara Noci 1, Tommaso A. Dragani 1*

1 Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

* Corresponding author. E-mail: dragani{at}istitutotumori.mi.it.

Received 6 March 2003 ; revised 9 April 2003 ; accepted 10 April 2003

Abstract

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. Since 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.

genetic susceptibility, inbred strains, lung tumors, Kras2
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