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Carcinogenesis Advance Access originally published online on April 24, 2003
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Carcinogenesis, Vol. 24, No. 6, 1143-1148, June 2003
© 2003 Oxford University Press

CARCINOGENESIS

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

The sequence data of D6Int38 are available from GenBank under accession number AY273192

Giacomo Manenti, Federica Galbiati, Sara Noci and Tommaso A. Dragani1

Department of Experimental Oncology, Istituto Nazionale Tumori, Via G. Venezian 1, I-20133 Milan, Italy

1 To whom correspondence should be addressed Email: dragani{at}istitutotumori.mi.it

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.


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