ORNITHINE DECARBOXYLASE ACTIVITY, CELL-PROLIFERATION, AND TUMOR PROMOTION IN MOUSE EPIDERMIS INVIVO

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (10) , 4183-4188
Abstract
The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate, as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis,4-trans-6,8-tetraenoylphorbol-13-acetate, strongly increased the activity of the enzyme and the intraepidermal level of putrescine (with a maximum at 5 h after application) when applied in doses which evoke comparable proliferative and irritant responses in skin. The hyperplasiogenic but nonirritant and almost nonpromoting 4-O-methyl ether of 12-O-tetradecanoylphorbol-13-acetate did not show such effects. Mechanical removal of the uppermost horny layer led to a considerable increase of ornithine decarboxylase activity after 4-8 h, while skin massage showed only a minute effect under conditions in which both treatments exhibited about the same mitogenic efficiency. Neither manipulation promotes tumor development. After skin massage, the induction of ornithine decarboxylase was influenced neither by treatments which alter the cyclic AMP level in epidermis (inhibition of phosphodiesterase, .beta.-adrenergic stimulation and injection of dibutyryl cyclic AMP) nor by injection of epidermal G1 chalone. No clear-cut correlation exists between epithelial cell proliferation, development of hyperplasia and tumor promotion and activation of epidermal ornithine decarboxylase.