GENETIC SUSCEPTIBILITY TO PAPILLOMA PROGRESSION IN SENCAR MICE

Previous results showed that in an inbred line (SSIN) derived from out bred SENCAR mice there is a dissociation between susceptibility to pap illoma development and the malignant conversion of these into squamous cell carcinomas (SCC), To extend this conclusion, we designed an inte rstrain breeding experiment using the two-step carcinogenesis protocol in order to study the susceptibility to tumor progression of F1 offsp ring, The strains used were SSIN, BALB/c, both known for their resista nce to papilloma progression, and SENCAR, Both the SSINxSENCAR and SEN CARxSSIN F1s showed a promotion sensitivity similar to that of the SSI N mice, This behavior was also seen in the SSINx(SSINxSENCAR) and SSIN x(SENCARxSSIN) backcrossed animals, suggesting that susceptibility to 12-O-tetradecanoylphorbol-13-acetate promotion under these protocol co nditions is inherited as a dominant trait. The BALB/cxSENCAR F1s showe d an average response that was intermediate between the two parental s trains/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 prem alignant progression, which is significatively delayed in SSIN mice co mpared with SENCAR mice, The SSINxSENCAR F1s expressed this switch in a way similar to the SENCAR mice, These findings suggest that suscepti bility to tumor progression is inherited as a dominant autosomal trait . The putative gene(s) that confers susceptibility is present in the S ENCAR stock and was probably lost in the selection and inbreeding of t he SSIN mice.