Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is possible to evaluate different dermatological therapeutic agents intended for human use in a variety of animal assays. This review will discuss some of these assays, and attempt to correlate animal and human skin responses. Psoriasis is a disease where changes in epidermal proliferation may be an important factor. It is possible to assay potential anti-psoriatic agents by measuring their ability to suppress DNA synthesis in the epidermis of hairless mice. This assay is predictive of the anti-psoriatic effectiveness of numerous agents including a variety of anti-proliferative drugs and anthralin, and has been used to evaluate the potential efficacy of purified coal tar shampoos and body preparations. The activity of the polyamine biosynthesis enzyme ornithine decarboxylase (ODC) is elevated in psoriatic skin, and it is induced in mouse epidermis by tape stripping. Retinoids can inhibit the induction of ODC activity, and this inhibition may be used to evaluate novel synthetic retinoids. Retinoids have beneficial effects on the abnormal keratinization found in various diseases. Rhino mice have multiple keratin-filled epidermal utricles, and the size of these is reduced by retinoid treatment. Observing the changes in the size of the utricles can be utilized to evaluate the effects of retinoids on keratinization. Sunscreen agents are tested on human volunteers by observing their ability to inhibit the erythema induced by exposure to solar-simulated light, to obtain a sun protection factor (SPF). It is possible to utilize the ability of sunscreens to inhibit other actinic-induced changes in the skin using animals. Parameters that may be measured include changes in DNA synthesis and ODC activity in the epidermis following ultraviolet irradiation. Some of these assays correlate well with human SPF determinations.
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PMID:Animal assays for anti-psoriatic, retinoid and sun protective agents. 637 47

8-Methoxypsoralen (8-MOP), 3-carbethoxypsoralen (3-CP), and 5-methoxypsoralen (5-MOP), with and without ultraviolet A (UVA), were compared as inducers of epidermal ornithine decarboxylase (ODC) and modulators of epidermal DNA synthesis in vivo in female Skh:hairless-1 albino mice. Both 8- and 5-MOP plus UVA induced epidermal ODC. Peak ODC activity was induced 24 hours after treatment, and ODC activity was still elevated at 48 hours. These same treatments also suppressed epidermal DNA synthesis 4 hours after treatment, as measured by tritiated thymidine incorporation. The psoralen 3-CP, which lacks the DNA monoadducts, failed to induce epidermal ODC either alone or with UVA and stimulated rather than suppressed incorporation of the tritiated thymidine.
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PMID:Psoralen and ultraviolet A effects on epidermal ornithine decarboxylase induction and DNA synthesis in the hairless mouse. 653 Oct 42

The ability of all-trans-retinoic acid (RA) and other retinoid derivatives to enhance DNA synthesis and to induce ornithine decarboxylase [L-ornithine carboxylyase; EC 4.1.1.17 (ODC)] activity has been investigated in normal and tape-stripped hairless mouse epidermis. Initial studies showed that the retinoids could inhibit the induction of epidermal ODC activity found 4.5 hr after tape stripping. Ten nmol RA, 13-cis-retinoic acid (13-cis-RA), ethyl-all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6, 8-nonatetraenoate (aromatic retinoid), or ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8, 8,-tetramethyl-2-naphthyl)-1-propenyl]benzoate (arotinoid ethyl ester) applied topically to the skin at 1 hr before tape stripping inhibited the induction of ODC activity. Induction of epidermal ODC activity was inhibited by arotinoid ethyl ester but not by RA, 13-cis-RA, or aromatic retinoid when they were applied to the skin at 24 hr prior to tape stripping. RA applied topically to normal hairless mouse skin induced a dose-dependent increase in epidermal ODC activity, detectable 24 hr or more after treatment. RA induced epidermal ODC activity to levels only 15- to 30-fold less than found after treatment with the potent tumor promoter tetradecanoylphorbol-13-acetate. Epidermal ODC activity was also induced by topical 13-cis-RA, aromatic retinoid, and arotinoid ethyl ester at this time, although in lower amounts than after RA treatment. The induction of ODC activity by RA was itself inhibited by topical arotinoid ethyl ester treatment. RA, 13-cis-RA, and aromatic retinoid induced ODC activity at doses below those required to enhance epidermal DNA synthesis. In summary, we have shown that, in common with other proliferative stimuli, retinoids can induce ODC activity in hairless mouse epidermis per se. Our results suggest that, because of their ability to also inhibit the expression of ODC activity, the induced ODC activity is found only after the retinoids have been depleted. The ability both to inhibit and to induce ODC activity may be related to the action of RA as a weak tumor promoter under certain conditions and as an inhibitor of promotion under others.
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PMID:Induction of ornithine decarboxylase activity and DNA synthesis in hairless mouse epidermis by retinoids. 661 53

Ornithine decarboxylase activity and polyamine concentrations were determined in the lungs of mice from 0 to 20 h after treatment with 12-O-tetradecanoylphorbol-13-acetate (17.7 nmol in 0.2 ml acetone/mouse). In CFLP mice, which responded to carcinogen with development of lung-adenomas, a single topical application of TPA to hairless mouse skin increased ornithine decarboxylase activity in the lung. In contrast, in C3H/He-mg mouse strain, which were resistant to lung-adenoma production, TPA application did not increase ODC activity of the lungs.
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PMID:Effect of 12-O-tetradecanoylphorbol-13-acetate on polyamine metabolism in mice sensitive and resistant to lung-adenoma. 661 64

Exposure of hairless mice to the light of a germicidal lamp (254 nm) under conditions which are known to induce epidermal DNA synthesis, cell proliferation, and polyamine metabolism produced a marked increase of polyamine excretion in the urine which lasted for many days. The increase was about the same for free and acetylated polyamines. Although the ratio of N1-acetylspermidine/N8-acetylspermidine increased somewhat in the urine of animals exposed to UV, the increase was not significant enough to be useful as a marker of enhanced cell proliferation. A single topical dose of alpha-difluoromethylornithine, a selective inhibitor or ornithine decarboxylase, prevented the UV-induced increase of polyamine excretion in agreement with its effect on UV-induced epidermal polyamine turnover.
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PMID:UV-induced changes in urinary polyamine excretion in the mouse. 678 80

In experimental studies of u.v.-skin-carcinogenesis u.v.-radiation is usually given in discrete amounts over a protracted period of time. Epidermal polyamine profiles were investigated in hairless mice after single and multiple exposures to ultraviolet-B (u.v.B). Hairless mice were irradiated with u.v.B from FS40 sunlamps and sacrificed after 1, 5, 10 or 20 days of daily irradiation with 0.9 kJ/sq m u.v.B at 6, 24 or 48 h after the final irradiation. Epidermis was analyzed for ornithine decarboxylase (ODC) activity, and for its putrescine, spermidine and spermine content. Skin biopsies were examined for histological changes. As previously reported epidermal ODC activity was induced 6 h after one irradiation with u.v.B and reached a maximum activity at approximately 24 h. In contrast after 5, 10 or 20 daily irradiations with u.v.B the epidermal ODC activity was maximal at approximately 6 h after the final irradiation and by 24 h had returned towards control levels. The magnitude of the ODC activity measured 6 h after irradiation increased with the number of irradiations. A similar pattern was seen with epidermal putrescine levels where a marked shift from a peak at approximately 24 h after one irradiation with u.v.B to a peak at approximately 6 h after 20 days of irradiation with u.v.B occurred. Spermidine levels increased as the number of u.v.B exposures was increased and spermine levels tended to decrease. The spermidine/spermine ratio increased most rapidly during the first 5 exposures, and remained elevated through to 20 days of daily irradiation. Chronic irradiation with u.v.B results in rapid induction of ODC activity and putrescine accumulation in the epidermis, events also elevated by chemical or viral transformation.
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PMID:Epidermal polyamine profiles after multiple exposures to ultraviolet radiation. 686 Dec 73

Sunscreens containing 5-methoxypsoralen (5-MOP) are currently being marketed to promote tanning by inducing psoralen-mediated ultraviolet (UV) A (320-400 nm) melanogenesis. The rationale is that this may prevent UVB (290-320 nm) radiation-induced skin damage. However, mouse studies have shown that 5-MOP has the same cutaneous photocarcinogenic potential as 8-methoxypsoralen. In addition, the 5-MOP--containing sunscreen Sun System III (SS III), when combined with UVA, induces epidermal ornithine decarboxylase activity, an enzyme associated with tumor promotion. Therefore, we investigated whether SS III had sufficient psoralen concentration to be tumorigenic in hairless mice exposed to chronic, intermittent UVA radiation. SS III was applied to hairless mice 5 days per week for 20 weeks. After each application the mice were exposed to 2.5 to 10 joules/cm2 UVA radiation. All test groups developed atypical squamous papillomas in direct proportion to the dosage of UVA radiation received. A shorter latency period for tumor development was seen with larger UVA doses. Test animals followed up to 1 year developed invasive squamous cell tumors. Control groups (SS III without UVA and UVA without SS III) remained free of tumors. Animals receiving SS III plus UVA developed persistent skin thickening and increased dermal cyst formation similar to that reported with chronic exposure to UVB, a known carcinogenic wavelength. Over-the-counter sunscreens containing 5-MOP do contain sufficient psoralen concentrations to cause cutaneous phototoxicity and photocarcinogenicity in mice, and their use in humans should be discouraged in the interest of preventing further UV-induced skin damage and skin cancer.
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PMID:Psoralen-containing sunscreen is tumorigenic in hairless mice. 686 46

The induction of ornithine decarboxylase (ODC) activity may be an essential component of skin tumor promotion. ODC requires pyridoxal 5'-phosphate (PLP) as a cofactor. We have measured the epidermal PLP concentration and investigated its relationship to DNA synthesis and ODC activity in the hairless mouse. The epidermal PLP concentration was approximately 1.0 microgram/g. When tape-stripping was used to induce ODC activity in the epidermis the concentration of PLP was significantly elevated 4.5 h later at the time of peak ODC activity and when DNA synthesis was reduced. Systemic treatment with the vitamin B-6 antagonist 4'-deoxypyridoxine (4-DOP) significantly reduced the epidermal PLP concentration and DNA synthesis. The ODC activity induced in the epidermis 4.5 after tape-stripping in 4-DOP-treated mice was only 17% of that induced in untreated tape-stripped controls. In in vitro experiments it was shown that while 4-DOP does not inhibit ODC activity, a major metabolite of 4-DOP-phosphate (Ki .06 mM), does. In mixing experiments it was shown that the epidermal extracts from 4-DOP-treated mice did not contain significant amounts of ODC inhibitors. 4-DOP may inhibit ODC induction in the epidermis by depleting the PLP content.
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PMID:Epidermal pyridoxal 5'-phosphate depletion, inhibition of DNA synthesis, and inhibition of the expression of ornithine decarboxylase activity by the vitamin B-6 antagonist 4'-deoxypyridoxine. 687 1

Two proprietary sunscreen preparations containing para-aminobenzoic acid and sulisobenzone, respectively, were tested for their ability to block the induction of ornithine decarboxylase by medium wavelength ultraviolet radiation (UV-B) in the epidermis of the hairless mouse. Both preparations were effective, the sunscreen treated animals requiring more radiation for ornithine decarboxylase induction. The UV dose-dependent gradients were reduced by a mean factor of 7.35 (sulisobenzone) and 15 (PABA). These figures correlate well with other in vivo sunscreen assays. This new method provides a simple and reproducible way of evaluating sunscreens in vivo.
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PMID:Sunscreens block the induction of epidermal ornithine decarboxylase by ultraviolet-B radiation: a new way of evaluating sunscreen efficacy in vivo. 698 Jun 60

Irradiation of skin with ultraviolet light of sunburn range (UVB) leads to a large and rapid induction of the polyamine biosynthetic enzyme ornithine decarboxylase in the epidermis. Induction of epidermal ornithine decarboxylase also occurs following application of the tumor promoting agent 12-0-tetradecanoylphorbol-13 acetate and topical retinoic acid is able to block both this ornithine decarboxylase induction and skin tumor promotion. In the studies described below, topical application of retinoic acid to hairless mouse skin leads to a significant inhibition of UVB-induced epidermal ornithine decarboxylase activity. The degree of this inhibition was dependent on the dose, timing, and frequency of the application of retinoic acid. To show significant inhibition of UVB-induced ornithine decarboxylase the retinoic acid had to be applied within 5 hr of UVB irradiation. If retinoic acid treatment was delayed beyond 7 hr following UVB, then no inhibition of UVB-induced ornithine decarboxylase was observed. The quantities of retinoic acid used (1.7 nmol and 3.4 nmol) have been shown effective at inhibiting 12-0-tetradecanoyl phorbol-13 acetate induced ornithine decarboxylase. The results show that these concentrations of topical retinoic acid applied either before or immediately following UVB irradiation reduces the UVB induction of epidermal ornithine decarboxylase. The effect of retinoic acid in these regimens on UVB-induced skin carcinogenesis is currently under study.
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PMID:Retinoic acid modulation of ultraviolet light-induced epidermal ornithine decarboxylase activity. 705 47


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