Comparison of some biochemical properties of epidermis in tumor promotion-susceptible and -resistant strains of mice.
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 xg supernatant was not significantly different between C57BL/6 and CD-1 mice. Protein kinase C activity of the 105,000 xg 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 TPA resides in a step distal to or other than the protein kinase C activation and ODC induction.
Yamamoto
S
S
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Kiyoto
I
I
Aizu
E
E
Sasakawa
N
N
Nakaki
T
T
Kato
R
R
D000818:Animals; D004790:Enzyme Induction; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate