dihydroteleocidin-b and Skin-Neoplasms

The activity of histidine decarboxylase (HDC) increased by a factor of 10 after a single application of 12-O-tetradecanoylphorbol-13-acetate (TPA). The HDC-inducing activity of other phorbol esters paralleled their tumor-promoting activity. Application of some indole alkaloids, which have been shown to be a new class tumor promoter, also induced the increase in HDC activity. The cell type responsible for this increase was examined. First, pieces of the skin were separated into epidermis and dermis after application of TPA. In contrast with ornithine decarboxylase, the HDC activity increased in the dermis. Second, genetically mast cell-deficient W/Wv and Sl/Sld mice were used. Although most histamine in the dermis is in the mast cells, the increase in HDC activity in W/Wv mice was comparable to that in congenic +/+ mice. However, no significant increase in HDC activity was detected in the skin of the Sl/Sld mice. Histological examination revealed that the magnitude of inflammatory cell infiltration was much less in the skin of Sl/Sld mice than in the skin of +/+ or W/Wv mice. The increase in HDC activity and the inflammatory cell response in the skin of W/Wv mice were abolished by prior X-ray irradiation, and were restored by subsequent bone marrow transplantation. Thus, inflammatory cells may be responsible for at least a part of the increase in HDC activity after application of tumor promoters.

Topics: Acrylamides; Animals; Carboxy-Lyases; Carcinogens; Cnidarian Venoms; Histamine; Histidine Decarboxylase; Leukocytes; Lyngbya Toxins; Mast Cells; Mice; Mice, Mutant Strains; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

Topics: Alkaloids; Animals; Carcinogens; Cell Adhesion; Cell Differentiation; Cocarcinogenesis; Enzyme Induction; Female; Lactones; Lyngbya Toxins; Mice; Neoplasms, Experimental; Ornithine Decarboxylase; Skin Neoplasms

The tumor-promoting effects of various doses of dihydroteleocidin B, a catalytically hydrogenated derivative of teleocidin B isolated from Streptomyces mediocidicus, were examined in a two-stage carcinogenicity test on mouse skin. Doses of 1.25, 2.5 and 5.0 micrograms of dihydroteleocidin B dissolved in 0.1 ml acetone were applied twice a week to 7,12-dimethylbenz[a]anthracene-initiated mouse skin for 30 weeks. The maximal cumulative tumor incidence, tumor yield, latent period for 50% cumulative tumor incidence (t50) and amount of promoter needed for 50% cumulative tumor incidence (D50) were used to assess tumor-promoting activity. A dose of 2.5 micrograms of dihydroteleocidin B had the maximal tumor-promoting activity. The optimal dose of dihydroteleocidin B for tumor-promoting activity coincided with the optimal dose for ornithine decarboxylase induction.

Topics: Alkaloids; Animals; Dose-Response Relationship, Drug; Female; Lyngbya Toxins; Mice; Neoplasms, Experimental; Skin Neoplasms

Dihydroteleocidin B, which is a derivative of teleocidin from Streptomyces, showed potent tumor-promoting activity in vivo when painted on mouse skin. Although the chemical structure of dihydroteleocidin B is entirely different from those of phorbol esters, the tumor-promoting activity of dihydroteleocidin B was found to be comparable to that of 12-O-tetradecanoylphorbol 13-acetate (TPA) in vivo. Teleocidin from Streptomyces and lyngbyatoxin A and debromoaplysiatoxin from the marine blue-green alga Lyngbya majuscula induced ornithine decarboxylase activity when painted on mouse skin, their effects being similar to those of dihyroteleocidin B and TPA. 13-cis-Retinoic acid inhibited this ornithine decarboxylase induction when painted on the skin 1 hr before these natural products. These three compounds produced adhesion of human promyelocytic leukemia cells (HL-60) to the flasks and inhibited differentiation of Friend erythroleukemia cells induced by dimethyl sulfoxide. The in vitro biological potencies of teleocidin and lyngbyatoxin A were almost as great as those of dihydroteleocidin B and TPA, but that of debromoaplysiatoxin was much weaker.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Alkaloids; Animals; Carcinogens; Cocarcinogenesis; Dermotoxins; Enzyme Induction; Female; Irritants; Lyngbya Toxins; Marine Toxins; Mice; Neoplasms, Experimental; Ornithine Decarboxylase; Skin Neoplasms; Structure-Activity Relationship