mezerein and Dermatitis--Contact

The ability of tumor promoters to suppress the development of contact hypersensitivity (CHS) was assessed by the mouse ear swelling assay. Application of the complete or second stage tumor promoters phorbol-12-myristate-13-acetate (PMA, 2 micrograms), croton oil (1%), benzoyl peroxide (20 mg), mezerein (2 micrograms), or phorbol-12-retinoate-13-acetate (PRA, 2 micrograms) to the abdominal surface of CF-1 female mice for 1 week (three treatments) prior to the sensitization of the same location with 0.5% 1-chloro-2,4-dinitrobenzene (DNCB) resulted in a 50% suppression (p less than 0.05) of the CHS response to DNCB. The first stage tumor promoters 4-O-Me-PMA (80 micrograms), calcium ionophore A23187 (80 micrograms), hydrogen peroxide (15%) and the non-promoting analogs phorbol-12,13-diacetate (PDA, 20 micrograms), phorbol (80 micrograms) or acetone did not suppress the response. The suppression of the development of CHS caused by PMA was dependent on the promoter being applied at the site of induction and was inhibited by application of the phospholipase A2 inhibitor dibromoacetophenone (100 micrograms), the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 100 micrograms), or the antiinflammatory steroid fluocinolone acetonide (2 micrograms). Application of PMA or mezerein 24 h prior to challenge with DNCB, to the ears of mice previously sensitized with DNCB resulted in a significant enhancement of the ear swelling response by 60% and 110%, respectively, compared with controls. The results demonstrate that tumor promoters suppress the development of CHS, and suggest the possibility that second stage promotion may involve suppression of the development of a tumor specific immune response.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Benzoyl Peroxide; Carcinogens; Dermatitis, Contact; Dinitrochlorobenzene; Diterpenes; Female; Immunosuppressive Agents; Mice; Terpenes; Tetradecanoylphorbol Acetate

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to beta-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Division; Cyclic AMP; Dermatitis, Contact; Diterpenes; Female; Isoproterenol; Mice; Neoplasms, Experimental; Ornithine Decarboxylase; Papilloma; Phorbol Esters; Phorbols; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate