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)

The purpose of this study was to examine the dose response and time course relationships between PUVA (psoralen + UVA) depletion of skin glutathione (GSH) and the induction of inflammation. Dorsal skin fold thickness (DSFT), an index of cutaneous edema, was used as a noninvasive measure of inflammation. Ornithine decarboxylase (ODC) was used as a measure of epidermal damage. Female hairless mice were given 8-methoxypsoralen (8-MOP) (dissolved in corn oil) by gavage at different doses, and 2 h later the mice were irradiated with 5 J/cm2 UVA. At 24 h, DSFT measurements were taken, the mice were killed, and reduced GSH, glutathione disulfide (GSSG), and glutathione-S-transferase were measured in the epidermis and dermis. Epidermal GSH was depleted 0, 11, 45, 87, and 98% from vehicle and/or UVA-treated levels (0.7 mM) after 0.1, 0.5, 5, 25, and 50 mg/kg, respectively. In the dermis GSH decreased from 0.3 mM by 47, 87, and 91% after 5, 25, and 50 mg/kg 8-MOP, respectively. Increases in DSFT of 20, 141, and 242% were observed after 5, 25, and 50 mg/kg doses, respectively. GSSG accounted for a small portion of total GSH in the skin after PUVA treatment. The maximal decreases in GSH were not observed until 24-48 h after PUVA treatment. PUVA treatment leads to dose-related increases in dermal edema, epidermal ODC, and depletion of GSH levels from both compartments in the skin. The time course of glutathione loss suggests that PUVA may interfere with its resynthesis or utilization from the circulation.
 ...
PMID:Depletion of cutaneous glutathione and the induction of inflammation by 8-methoxypsoralen plus UVA radiation. 287 29

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.
 ...
PMID:Psoralen and ultraviolet A effects on epidermal ornithine decarboxylase induction and DNA synthesis in the hairless mouse. 653 Oct 42

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.
 ...
PMID:Psoralen-containing sunscreen is tumorigenic in hairless mice. 686 46

Sunscreens containing 5-methoxypsoralen (5-MOP) are being promoted commercially to increase suntanning and sun protection. A recent study indicated that the 5-MOP concentration used in these sunscreens is too low to induce cutaneous phototoxicity with ultraviolet (UV) radiation. We investigated whether the sunscreen Sun System III (SS III), which contains 5-MOP, could induce skin erythema, edema, delayed pigmentation, and epidermal ornithine decarboxylase (ODC) activity when used in conjunction with UVA radiation (320-400 nm). ODC induction is an early event in the promotion of skin tumors. Increased epidermal ODC activity has been reported after exposure to UVB radiation (290-320 nm) alone and with topical 8-methoxypsoralen (8-MOP) plus UVA radiation. Using a solar simulator, we found SS III-induced erythema, edema, and epidermal ODC activity in hairless mouse skin with only 5 joules/cm2 of UVA. Human skin showed erythema and delayed pigmentation with SS III plus 20 joules/cm2 of UVA. No phototoxicity was seen in human skin unless the solar simulator output was filtered through water to reduce infrared radiation. This indicates that cutaneous phototoxic reactions to 5-MOP plus UVA are diminished by heat. Like 8-MOP, 5-MOP cross-links DNA and has the same skin photocarcinogenic potential as 8-MOP. Therefore the use of phototoxic psoralens in over-the-counter sunscreens is inappropriate because of the risk of increased UV-induced skin cancer.
 ...
PMID:Psoralen-containing sunscreen induces phototoxicity and epidermal ornithine decarboxylase activity. 709 64

Epidermal thymidine incorporation, as a measure of DNA synthesis, and ornithine decarboxylase activity were estimated in hairless albino mice following phototoxic reactions induced by topical anthracene + UV-A, and topical 8-methoxypsoralen (8-MOP) + UV-A. Both treatments caused depression of epidermal thymidine incorporation to 26% of control values at 4 h; this depression persisted through 24 h following 8-MOP + UV-A. Animals treated with anthracene + UV-A showed a fourfold increase in thymidine incorporation at 48 h, declining at 72 and 96 h; after 8-MOP + UV-A increased thymidine incorporation was observed between 4 and 10 days, when a plateau of 96 h duration was observed. After treatment with anthracene + UV-A, epidermal ornithine decarboxylase activity (ODC) was maximal at 4 h, and exhibited a rapid decline, with normal levels at 48 h. Following 8-MOP, UV-A dose-dependent ODC induction occurred: this was later than that induced by anthracene + UV-A with no detectable activity at 4 or 12 h, and maximum activity at 24 h, the elevation persisting through 96 h. The relationship between ODC induction and epidermal hyperproliferation following these treatments is discussed.
 ...
PMID:Epidermal ornithine decarboxylase activity and thymidine incorporation following treatment with ultraviolet A combined with topical 8-methoxy-psoralen or anthracene in the hairless mouse. 727 5

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm2). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm2). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis.
 ...
PMID:Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse. 797 49