Susceptibility of 129/SvEv mice in two-stage carcinogenesis protocols to 12-O-tetradecanoylphorbol-13-acetate promotion

Embryonic stem cells derived from various derivatives of the murine 129/J strain are commonly used in the generation of knockout mice. Topical twice-weekly treatment of the 129/SvEv subline with either 2 or 5 microg of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 4 weeks resulted in a sustained inflammation and hyperplasia. Identically treated C57BL/6 mice developed weaker inflammatory and hyperplastic responses over the same treatment course, and did not exhibit a sustained hyperplasia. SSIN mice treated with either 0.5 or 2 microg of TPA developed a sustained hyperplasia comparable to that seen in 129/SvEv mice, but a weak inflammatory response. Myeloperoxidase (MPO) measurements indicated dramatic infiltrations of the skins of all three murine strains by neutrophils within 48 h of a single TPA application. MPO activities remained significantly elevated in the skins of 129/SvEv mice and C57BL/6 mice following eight TPA treatments. In contrast, MPO activities in 8 X treated SSIN skins were comparable to those measured in solvent controls. 129/SvEv mice readily developed papillomas in two-stage skin carcinogenesis protocols employing DMBA as the initiator and TPA as the promoter. Papilloma incidences and multiplicities were dose-responsive with respect to promoter (using twice weekly applications of 1, 2 or 5 microg of TPA). With a promoting dose of 5 microg of TPA > or = 90% of the mice developed papillomas within 13 weeks, and maximum tumor multiplicities were reached within 18 weeks. These latter results, when compared to the published responses of other murine stocks and strains, demonstrate that 129/SvEv mice are very sensitive to TPA promotion in two-stage skin carcinogenesis protocols.