Genetic susceptibility to papilloma progression in SENCAR mice.
Previous results showed that in an inbred line (SSIN) derived from outbred SENCAR mice there is a dissociation between susceptibility to papilloma development and the malignant conversion of these into squamous cell carcinomas (SCC). To extend this conclusion, we designed an interstrain breeding experiment using the two-step carcinogenesis protocol in order to study the susceptibility to tumor progression of F1 offspring. The strains used were SSIN, BALB/c, both known for their resistance to papilloma progression, and SENCAR. Both the SSIN X SENCAR and SENCAR X SSIN F1s showed a promotion sensitivity similar to that of the SSIN mice. This behavior was also seen in the SSIN X (SSIN X SENCAR) and SSIN X (SENCAR X SSIN) backcrossed animals, suggesting that susceptibility to 12-O-tetradecanoylphorbol-13-acetate promotion under these protocol conditions is inherited as a dominant trait. The BALB/c X SENCAR F1s showed an average response that was intermediate between the two parental strains/stocks. Regarding the progression, all F1s showed a cumulative number of SCCs similar to the SENCAR progenitor. We also investigated the previously described switch of keratin 1 to 13 as a marker of premalignant progression, which is significatively delayed in SSIN mice compared with SENCAR mice. The SSIN X SENCAR F1s expressed this switch in a way similar to the SENCAR mice. These findings suggest that susceptibility to tumor progression is inherited as a dominant autosomal trait. The putative gene(s) that confers susceptibility is present in the SENCAR stock and was probably lost in the selection and inbreeding of the SSIN mice.
Stern
M C
MC
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA.
Gimenez-Conti
I B
IB
Conti
C J
CJ
D000818:Animals; D005260:Female; D006824:Hybridization, Genetic; D051379:Mice; D008807:Mice, Inbred BALB C; D010212:Papilloma / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D013755:Tetradecanoylphorbol Acetate