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.
Saran
Anna
A
ENEA CR Casaccia, Rome, Italy.
Zaffaroni
Daniela
D
Pazzaglia
Simonetta
S
Peissel
Bernard
B
Galbiati
Federica
F
Spinola
Monica
M
Manenti
Giacomo
G
Zanesi
Nicola
N
Rebessi
Simonetta
S
Mancuso
Maria Teresa
MT
Covelli
Vincenzo
V
Dragani
Tommaso A
TA
D000483:Alleles; D000818:Animals; D021461:Animals, Outbred Strains; D015197:Carcinogenicity Tests; D002273:Carcinogens; D005260:Female; D020022:Genetic Predisposition to Disease; D007178:Inbreeding; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D010212:Papilloma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012878:Skin Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate; D014520:Urethane; D018631:ras Proteins
D002273:Carcinogens; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D014520:Urethane; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate