Inhibition of both skin and lung tumorigenesis by Car‐R mouse‐derived cancer modifier loci

The Car-R outbred mouse line was phenotypically selected for high resistance to two-stage skin tumorigenesis. In the present study we tested the hypothesis that a subset of genetic loci responsible for resistance to skin tumorigenesis of Car-R mice might also inhibit lung tumorigenesis. Skin and lung tumorigenesis were induced in groups of Car-R, SWR/J, (SWR/JxCar-R)F1 and SWR/Jx(SWR/JxCar-R) backcross mice by i.p. urethane initiation and skin TPA promotion. Car-R mice showed a much lower susceptibility to both skin and lung tumorigenesis as compared to SWR/J mice, which are susceptible to both lung and skin tumorigenesis. The Car-R-inherited genome significantly inhibited both skin and lung cancer development in the F1 progeny of Car-R with SWR/J mice. In the backcross population, skin and lung tumor phenotypes showed a statistically significant correlation, indicating that a subset of the cancer resistance alleles, which segregated in the Car-R line during selection for resistance to skin carcinogenesis, provides resistance to both skin and lung tumorigenesis.