Comparison of Some Biochemical Properties of Epidermis in Tumor Promotion-Susceptible and -Resistant Strains of Mice

[摘要] References(18)Cited-By(2)It has been reported that CD-1 and SENCAR mice are susceptible and C57BL/6 mice are resistant to skin tumor promotion caused by phorbol esters. Specific binding of a phorbol ester to its epidermal receptor site, epidermal protein kinase C activity, and ornithine decarboxylase (ODC) induction in epidermis were compared between tumor promotion-susceptible and -resistant strains of mice. Specific binding of[3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to the particulate fraction of the epidermis of C57BL/6 mice gave a similar dissociation constant (Kd) and a maximal number of binding sites (Bmax) to those of CD-1 mice. Protein kinase C activity of the epidermal 105, 000×g supernatant was not significantly different between C57BL/6 and CD-1 mice. Protein kinase C activity of the 105, 000×g pellet, however, was significantly higher in C57BL/6 mice than in CD-1 mice. A topical application of TPA to the skin caused epidermal ODC induction in all of these strains of mice. At any doses of TPA, TPA-induced epidermal ODC activity of C57BL/6 mice was always higher than those of SENCAR and CD-1 mice. Maximal induction of epidermal ODC by TPA was also highest in C57BL/6 mice among these three strains of mice. These results indicate that the mechanism of the difference in susceptibility of C57BL/6, CD-1 and SENCAR mice to the tumor-promoting action of TPA resides in a step distal to or other than the protein kinase C activation and ODC induction.

[学科分类] 药理学