Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palytoxin is a human and mouse skin irritant and complete mouse skin tumor promoter that differs from the well-studied phorbol ester class of tumor promoters in many respects. In this study, we have found palytoxin to stimulate the production of superoxide by isolated human neutrophils using electron paramagnetic resonance (EPR) spectroscopy with the spin-trap DMPO. This stimulation of oxyradical production by palytoxin is relatively weak, however, when compared to that by 12-O-tetradecanoylphorbol-13-acetate (TPA). The maximal amount of oxyradicals produced by palytoxin-stimulated neutrophils is 10(-4) mumols/10(6) neutrophils, and this stimulation requires nanomolar concentrations of palytoxin, with half maximal stimulation at concentrations of approximately 30 nM. In contrast, the tumor promoter TPA causes human neutrophils to generate in excess of 10(-3) mumols oxyradicals/10(6) neutrophils with concentrations as low as 1 nM. Toxicity to cultured human epidermal cells was observed at very low concentrations of palytoxin, with 50% loss of colony-forming efficiency observed at approximately 3 x 10(-13) M. For TPA, 50% loss of colony-forming efficiency for cultured epidermal cells requires approximately 5 nM. Thus, although palytoxin stimulates superoxide production in isolated neutrophils, epidermal cells are sensitive at much lower concentrations and are likely to be the important target cell in vivo. This is in contrast to TPA, where neutrophils are stimulated at concentrations less than those required to produce pathological effects on epidermal cells, suggesting that neutrophils may be an important target cell for TPA in vivo.
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PMID:Measurement of neutrophil activation and epidermal cell toxicity by palytoxin and 12-O-tetradecanoylphorbol-13-acetate. 135 52

Bilobol, isolated from ginkgo fruit pulp, has been noted to be a strong skin irritant like 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoter in the skin. A comparative investigation of morphological changes induced by bilobol and TPA induced in the skin of CD-1 mice, and an assessment of the skin tumor promoting potential of bilobol were therefore performed. In experiment I, mice received a single application of 2.5, 50 or 1000 micrograms of bilobol, or 0.1 or 2.5 micrograms of TPA on the right ear. The 50 or 1000 micrograms bilobol and 2.5 micrograms TPA doses caused ear redness, epidermal thickening and inflammatory infiltration. The dose of 2.5 micrograms of TPA, which is usually used as tumor promoter in skin carcinogenesis, was equivalent to 50 micrograms of bilobol in irritant effect. Thus, 50 micrograms of bilobol was used for the promotion testing (experiment II) in CD-1 mice initiated with 100 micrograms of 7, 12-dimethylbenz[a]anthracene (DMBA). Treatment with either 10 or 50 micrograms bilobol twice a week for 30 weeks did not result in any tumor development, thus suggesting that bilobol is not a complete promoter of skin carcinogenesis, despite generation of inflammation.
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PMID:Comparison of the effects of bilobol and 12-O-tetradecanoylphorbol-13-acetate on skin, and test of tumor promoting potential of bilobol in CD-1 mice. 211 May 95

Eight skin irritant 3-esters with the homologous even number aliphatic acids (acetic to hexadecanoic acid) of the polyfunctional diterpene alcohol ingenol as well as the non-irritant 3-tetradecanoate of delta 7,8-isoingenol were tested for their initiation or (tumor)-promoting activity in the standardized semi-quantitative initiation/promotion assay on the back skin of NMRI mice. In a corresponding protocol over 48 weeks without preceding initiation, i.e. as a tumorigen, the 3-hexadecanoate of ingenol (3-HI) proved to be practically inactive as compared to the strong response elicited as promoter. Dose/response relations were shown to be positive for both 3-HI and 3-O-tetradecanoylingenol (3-TI), as representative ingenol-3-esters. In assays for structure/activity relations of promoting activity, it turned out that the group of 3-acetate, 3-butyrate and 3-hexanoate of ingenol are very weak to weak promoters. The group of 3-octanoate to 3-HI proved to be strong promoters. Maximal activity was exhibited by 3-TI and it is proposed that this be considered the prototype of the 3-esters of the ingenane type. In semi-quantitative terms it is slightly less active as a skin tumor promoter than the tigliane type 12-O-tetradecanoylphorbol-13-acetate. At the same dose level as 3-TI, the 3-tetradecanoate of delta 7,8-isoingenol was inactive as a promoter.
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PMID:Structure/activity relationships of polyfunctional diterpenes of the ingenane type. I. Tumor-promoting activity of homologous, aliphatic 3-esters of ingenol and of delta 7,8-isoingenol-3-tetradecanoate. 310 81