Epidermal ornithine decarboxylase activity

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 12-0 -tetradecanoylphorbol-13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there is evidence for a dual effect of mirex during co-promotion first, as an independent tumor promoter with a mechanism different than that of phorbol esters and second, as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). 

ZO024 Park, K. K., K. S. Chum, ]. M. Lee, S. S. Lee, and Y. ]. Surh. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett 1998 129(2) 139-144. 

Agarwal, R. et al.. Inhibitory effect of silymarin an antihepatotoxic flavonoids on TPA-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice. Carcinogenesis, 15, 1099, 1994. 

Park, K.-K. Chun, K.-S., Lee. J.-M.. Lee, S.S., and Surh, Y.-J. (1998) Inhibitory Effects of [6]-Gingerol, a Major Pungent Principle of Ginger, on Phorbol Ester-Induced Inflammation, Epidermal Ornithine Decarboxylase Activity and Skin Tumor Promotion in ICR Mice, Cancer Lett. 129,139-144. 

Inhibition of mouse epidermal ornithine decarboxylase activity induced by phorbol ester— topical dosage of single dose of retinoid (ED50, nmol)... 

Tazarotene (Tazorac) is a third-generation retinoid approved for the treatment of psoriasis and acne vulgaris. This retinoid binds to aU three RARs. In mice, tazarotene blocks ornithine decarboxylase activity, which is associated with cell proliferation and hyperplasia. In cell culmre, it suppresses markers of epidermal inflammation and inhibits comification of the keratinocyte. 

Studies of the methanolic extract of Alpinia oxyphylla have shown that this extract suppresses the promotion of skin tumors in mice and that it induces apoptosis in cultured human promyelocytic leukemia cells. In addition, two phenolic diarylheptano ids isolated from the active extract, yakuchinone A and yakuchinone B, were found to ameliorate tumor promotion as well as inhibit both TPA-induced epidermal ornithine decarboxylase (ODC) activity and ODC RNA expression. Moreover, yakuchinones A and B reduced production of the TNF-a in the TPA-stimulated skin of mice. Furthermore, both compounds inhibited the TPA-induced expression of COX-2 at both transcriptional and... 

It may at first appear paradoxical that diseases such as psoriasis and lamellar ichthyosis, which are characterized by a hyperproliferative epidermis, can benefit from dmgs such as the retinoids, which can stimulate epidermal proliferation under certain experimental conditions. However, when tested in patients with psoriasis, etretinate led to decreased ornithine decarboxylase activity, decreased levels of urinary and cutaneous polyamines, and decreased epidermal DNA synthesis (Kaplan et al., 1983). 

RLV/Fischer rat assay without the addition of an exogenous metabolic activation system. In a single study, mouse JB6 epidermal cells were transformed by di(2-ethyl-hexyl) phthalate without activation and in one of two studies a weak response was reported in the CSHIOT A cell transformation assay with di(2-ethylhexyl) phthalate in either the absence or presence of exogenous metabolic activation. BALB/c-3T3 cells were not transformed by di(2-ethylhexyl) phthalate with or without metabolic activation. Di(2-ethylhexyl) phthalate inhibited gap-junctional intercellular communication in Chinese hamster V79 cells in six of seven studies, but not in one study of liver cells of cynomolgus monkeys in vivo. Di(2-ethylhexyl) phthalate treatment of Syrian hamster embryo cells in a two-stage exposure with 12-O-tetradecanoylphorbol 13-acetate resulted in superinduction of ornithine decarboxylase, an early event in morphological transformation no effect was seen after a one-stage treatment with di(2-ethylhexyl) phthalate alone. 

Rosemary (Rosmarinus officinalis) contains flavonoids, phenols, volatile oil and terpenoids. Topical application of rosemary extract, carnosol or ursolic acid to mouse skin inhibited the covalent binding of benzo[a]pyrene to epidermal DNA (Huang et al. 1994), tumour initiation by 7,12-dimethylbenz [ajanthracene (Singletary and Nelshoppen 1991), 12-0-tetradecano)dphorbol-13-acetate-induc-ed tumour promotion, ornithine decarboxylase (EC 4.1.1.17) activity and inflammation. Carnosol showed potent antioxidative activity in a,a-diphe-nyl-P-picrylhydrazyl free radicals scavenge and DNA protection from Fenton reaction (Lo et al. 2002). 

Mineral fibers, particularly asbestos, can activate protein kinase C and increase expression of ornithine decarboxylase, the proto-oncogenes, c-fos, and c-jun (18-20), and the nuclear transcription factor, NF-kB (21). All these events are associated with cell proliferation and, potentially, with neoplastic transformation. Recently, Zanella et al. (22) have shown that asbestos activates the mitosis-associated kinase (MAP) system, apparently through interaction with the epidermal growth factor receptor, probably implying that some of these events are mediated by signal transduction pathways that start on the cell surface, rather than by fiber uptake, although this point needs to be directly examined. 

---