title: Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains.
abstract: Lung tumor susceptibility in inbred mouse strains is caused by the susceptibility allele at the pulmonary adenoma susceptibility 1 (Pas1(s)) locus. However, after urethane treatment, most strains carrying the Pas1(s) allele show an intermediate (1-4 tumors/mouse) instead of a highly susceptible (15-30 tumors/mouse) lung tumor phenotype. To test the hypothesis that strains displaying the intermediate lung tumor phenotype carry dominant or codominant resistance alleles at pulmonary adenoma resistance (Par) loci, we crossed mice of intermediate susceptibility or resistance to lung tumorigenesis with the highly susceptible A/J strain. Eleven F(1) hybrids were treated with urethane to induce lung tumorigenesis. The A/J strain developed 35.3 tumors/mouse, while its F(1) hybrid with C57BL/6J mice (null allele at Par loci) developed 22.8 tumors/mouse due to the Pas1 allele dosage effect. F(1) hybrids of strains 129/SvJ, CBA/J, ST/J and LP/J (Pas1(s)) and of SPW, DBA/2J and C57L/J (Pas1(r)) mice showed significant reduction in lung tumor multiplicity (i.e., 0.3-12.8 tumors/mouse) compared to A/J and (A/J x C57BL/6J)F(1) mice. These results indicate that resistance alleles at Par loci are common in inbred mouse strains and account for the lung tumorigenesis intermediate phenotype of strains carrying the Pas1(s) allele.
authors: Department of Experimental Oncology, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy.
authors: Giacomo
authors: G
authors: Manenti
authors: Abraham
authors: A
authors: Acevedo
authors: Federica
authors: F
authors: Galbiati
authors: Roberto
authors: R
authors: Giannì Barrera
authors: Sara
authors: S
authors: Noci
authors: Eduardo
authors: E
authors: Salido
authors: Tommaso A
authors: TA
authors: Dragani
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002273:Carcinogens; D018628:Gene Dosage; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D010641:Phenotype; D014520:Urethane
chemical_list: D002273:Carcinogens; D014520:Urethane