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

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. 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.