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)

Application of the alkane n-dodecane to the dorsal skin of 6-8 week old female SENCAR mice initiated with 10 nmol dimethylbenz[a]anthracene led to papilloma formation in the majority of treated animals. Compared to the potent phorbol diester 12-O-tetradecanoylphorbol-13-acetate (TPA), n-dodecane was several orders of magnitude less potent on a dose basis, and maximal papilloma response required more extended application (22 weeks for 50 mg dodecane compared to 12 weeks for 2 micrograms TPA). In two-stage promotion experiments n-dodecane appeared to act as a stage II promoting agent at appropriate doses, being comparable in activity to mezerein--an agent with well-characterized activity of this type. Dodecane, unlike mezerein, did not induce the formation of a significant number of pyknotic cells, however, suggesting that the weak promoting activity of dodecane in stage 1 was not a result of toxicity. In comparison with TPA, both mezerein and n-dodecane at promoting doses induced less sustained hyperplasia in SENCAR mouse skin, a finding also consistent with the proposal that n-dodecane is principally active in stage II of two-stage promotion models. Both agents induced ornithine decarboxylase activity in SENCAR mouse skin, the maximal induction being observed at apparently the same time after a single application.
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PMID:Mechanism of mouse skin tumor promotion by n-dodecane. 367 5

Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2 x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that precluded any meaningful analysis of short-term biomarkers in relationship to biological activity.
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PMID:Short-term biomarkers of tumor promotion in mouse skin treated with petroleum middle distillates. 984 20