Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single topical application of 17 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the skin of hairless mice induces characteristic transient alterations in the epidermal cells turnover and maturation (0.96 h), associated in time with characteristic changes in the activities of L-ornithine carboxy-lyase (E.C. 4.1.1.17) (ODC) and S-adenosyl-L-methionine carboxy-lyase (E.C.4.1.1.50) (SAM-D) and in the accumulation of polyamines. The effects on these responses of local pretreatment of the skin with retinoic acid 1 h prior to TPA were investigated at selected time points. Retinoic acid inhibited the TPA-induced ODC activity and the ensuing accumulation of putrescine, but did not alter the TPA-induced SAM-D activity or the molar ratio of spermidine/spermine. This pretreatment also decreased in number of dividing basal cells in the first TPA-induced synchronized wave of proliferating cells. However, during the subsequent period of proliferation, the number of dividing cells in the retinoic acid pretreated group was comparatively increased. Hence, at four levels of retinoic acid (0.17, 1.70, 17.0 and 170 nmol), which all inhibited the TPA-induced ODC effectively, there was no change in the total number of basal cells that divided during 16-48 h after TPA-application. Theory is put forward the retinoic acid might exert its antitumorigenic effect during tumor promotion with TPA by interfering with the rate and/or quality of epidermal cell maturation, rather than by inhibiting cell proliferation.
Carcinogenesis 1982
PMID:Effect of retinoic acid pretreatment on 12-O-tetradecanoylphorbol-13-acetate-induced cell population kinetics and polyamine biosynthesis in hairless mouse epidermis. 708 72

Groups of hairless mice were treated with 4 skin applications of 470 nmol 3-methylcholanthrene (MCA) in benzene and 4 of 20 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) in various sequences, twice a week, together and separately. Three days after the last application, cell kinetic investigations were made comprising the counting of basal and suprabasal cells, the assessment of hyperplasia, the mitotic rate by the stathmokinetic method, the labelling index and the specific activity of DNA after injection of a dose of [3H]dT, and the determination of percentage of cells in each cell-cycle phase by flow cytometry. These studies showed that various treatment schedules with 4 applications stimulated proliferation and caused epidermal hyperplasia, but there was no significant difference between the groups in degree of growth stimulation. There was a significantly higher tumour production by all the combinations than by MCA alone. It was of no significant importance for the tumour production whether the 4 applications of MCA came before or after the 4 of TPA. Alternating treatment (MCA-TPA, etc.) seemed to give a higher tumour risk than the other treatment sequences. The consequences of these results for the two-stage theory of carcinogenesis (stating that initiation must come first) are discussed, and it is concluded that (at least under the experimental conditions used here) initiation does not need to come first for a good tumour yield.
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PMID:Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. 709 24

Modulation of ultraviolet-B (UVB) skin carcinogenesis by topical treatment with two antiinflammatory drugs expected to have different mechanisms of action has been studied in the hairless mouse. Indomethacin is a nonsteroidal antiinflammatory agent which may act by inhibiting prostaglandin biosynthesis. Triamcinolone acetonide is a steroidal antiinflammatory agent. Both of these drugs inhibited the induction of epidermal ornithine decarboxylase by UVB when applied topically in a acetone vehicle. A UVB skin tumor study was designed. Groups of mice were irradiated daily with UVB for 20 days, each mouse receiving a total of 17.1 kJ UVB per sq m. Group 1 was treated with acetone immediately after each irradiation; Group 2 received 700 nmol indomethacin in acetone immediately after each irradiation; Group 3 received 14.4 nmol triamcinolone acetonide in acetone immediately after each irradiation. Mice were killed after 52 weeks, and the tumors were excised and examined histologically. Both topical indomethacin and topical triamcinolone acetonide were effective in reducing the incidence and size of the skin tumors induced by UVB. This evidence supports the hypothesis that the induction of ornithine decarboxylase may be a critical component of UVB skin carcinogenesis and that inhibition of ornithine decarboxylase induction can be used as a screen for agents which will inhibit UVB skin carcinogenesis.
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PMID:Inhibition of ultraviolet-B epidermal ornithine decarboxylase induction and skin carcinogenesis in hairless mice by topical indomethacin and triamcinolone acetonide. 710 93

To study the relationship between epidermal DNA synthesis and carcinogenesis, groups of hairless mice were given a single skin application of 2 mg N-methyl-N-nitrosourea (MNU) in acetone. One group received no pretreatment, another group was injected i.p. with 5 mg hydroxyurea (HU) 30 min before MNU, and a further group with 0.5 mg Colcemid 3 h before MNU. Other groups were injected i.p. 14 and 4 h before MNU with either saline, 5 mg crude aqueous skin extract, 2 mg dialysed skin extracts of two types, or 2 mg dialysed extracts of liver or heart muscle, respectively. All substances were dissolved in 0.5 ml distilled water. Cell kinetic studies showed that the three skin extracts inhibited epidermal DNA synthesis and mitosis. HU inhibited DNA synthesis and increased the mitotic rate. The other pretreatments had no effect on epidermal DNA synthesis. There was a significant enhancement of the production of skin tumors in the groups pretreated with epidermal extracts or HU. MNU is a short-acting carcinogen with a half-life in the cell of 30 min. Hence, the results show that when DNA synthesis is inhibited at the time of MNU application, more tumors are produced in the skin. A possible explanation of the enhancement is that a compensatory wave of proliferation a short time after carcinogen binding may fix a DNA injury before repair can take place.
Carcinogenesis 1982
PMID:Enhancement of methylnitrosourea skin carcinogenesis by inhibiting cell proliferation with hydroxyurea or skin extracts. 712 69

To study the relationship between epidermal DNA synthesis and carcinogenesis, hairless mice of both sexes were given a single topical application of 1 mg N-methyl-N-nitrosourea (MNU) in acetone. A control group received only MNU, whereas other groups were injected i.p. with 5 mg hydroxyurea (HU), 1 h, 45 min and 15 min before, simultaneously with, and 15 min, 30 min and 45 min after MNU application. The production of skin tumors was recorded and the results were assessed with accepted statistical methods. Injection of HU shortly before a single application of MNU enhanced skin carcinogenesis, and when HU is injected 30 min before MNU, the enhancement seems to be most pronounced. HU administered simultaneously with or following MNU application, did not alter the production of tumors. The cell kinetic situation in the epidermis at the time of a carcinogen application, and the modulation of the cell kinetic reaction to the carcinogen by any type of post- or pretreatment, may influence tumorigenesis.
Carcinogenesis 1982
PMID:Hydroxyurea enhances methylnitrosourea skin tumorigenesis when given shortly before, but not after, the carcinogen. 712 70

A new synthetic psoralen (5'aminomethyl-4,4',8-trimethylpsoralen) is presented which possesses potential superior photochemotherapeutic efficacy. Results of studies conducted on the guinea pig and hairless mouse in our laboratories reveal that following oral administration there is a more rapid onset of photosensitization, a more rapid loss of photosensitization indicating apparent chemical inactivation or excretion, and a lower systemic toxicity on a milligram to milligram basis when compared to conventional psoralen derivatives. These results indicate that the use of this new derivative will minimize potential side effects such as ocular complications and inadvertent additional photosensitization that might lead to premature aging and carcinogenesis due to the slow onset and prolonged photosensitization following administration that are characteristic of conventional psoralen derivatives.
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PMID:Photochemotherapy: a new promising chemical derivative. 716 33

The effects of all-trans retinoic acid (RA) in 0.05%, 0.025% and 0.005% concentrations on ultraviolet (UV) induced carcinogenesis was investigated in the skin of Uscd strain hairless mice. A carcinogenic amount of UV energy was delivered over the 12-mo period of the study. The 0.025% and 0.005% RA solutions did not alter the development of cutaneous cancers. However, the 0.05% RA concentration significantly inhibited the tumor formation in this study.
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PMID:Inhibition of ultraviolet-induced carcinogenesis by all-trans retinoic acid. 724 Jul 86

This paper reviews factors that have been reported to influence photocarcinogenesis in laboratory animals. Such factors include the sensitivity of the test animals, the amount of the ultraviolet radiation (UVR) delivered, the mode of its delivery, and interactions of other radiations or of chemicals in the process of carcinogenesis. New data are presented in these areas: reduction in the size of each unit dose (and thus an increase in dosing frequency) increases the carcinogenic effectiveness of a given lifetime dose; certain inbred strains of albino hairless mice exhibit heritable differences in their susceptibility; several chemicals are known to enhance photocarcinogenesis, but they appear to have so little in common, either structurally or functionally, that they offer limited guidance about which other compounds may be effective in this way. Prevention of long-term UVR effects on skin is a desirable goal; development of personal UVR dosimeters will aid in defining the quantitative nature of the problem; improved sunscreens should provide the means to achieve significant reduction in the incidence of UVR-induced human skin cancer.
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PMID:Photocarcinogenesis: an overview. 725 47

A single application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to hairless mouse skin induces increased activity of epidermal L-ornithine carboxy-lyase (E.C.4.1.1.17) (ODC) with a peak at 5 h, and S-adenosyl-L-methionine carboxy-lyase (E.C.4.1.1.50) (SAM-D) with a broad peak at 20-36 h. The temporal sequence of the accumulation of polyamines; i.e. putrescine, spermidine and spermine, and the rate of DNA synthesis was investigated. All four parameters were measured in the same tissue-samples and multiple peaks of DNA synthesis and of individual polyamines were demonstrated. In the period from 0-12 h, there was an initial decrease in the rate of DNA synthesis. In this period changes in the molar ratio of spermidine/spermine were negatively correlated to the rate of DNA synthesis. From 12-48 h, however, changes in the molar ratio of spermidine/spermine had an almost identical time course with rates of change of DNA synthesis. Based on corresponding cell kinetic results it is suggested that the spermidine/spermine ratio reaches a maximum peak during the S-phase of the cell cycle. The relation between the rate of DNA-synthesis and the spermidine/spermine ratio as well as the ordered time sequence for the accumulation of putrescine and the induction of ODC and SAM-D activities, suggest a strong interdependence and a strict regulation of these events in hairless mouse epidermis induced to proliferate by TPA.
Carcinogenesis 1981
PMID:Changes in epidermal polyamine biosynthesis and specific activity of DNA following a single application of 12-O-tetradecanoyl-phorbol-13-acetate to hairless mouse skin. 727 34

The carcinogenic and melanogenic effects of a filtered metal halide source (UVASUN) that emits UV radiation in a range from 340 to 400 nm and a bank of Philips TL 09R tubes (TL 09) emitting in a range from 310 to 400 nm were studied in lightly pigmented hairless hr/hr C3H/Tif mice. Both the carcinogenic effect of the two UVA radiation sources alone and in combination with a UV source, consisting of one Philips TL 12 and five Bellarium-S SA-1-12 tubes emitting radiation somewhat similar to the UV part of the solar spectrum (SOLAR UV), were investigated. Finally, the melanogenic effect of exposure to the two UVA sources were studied. The mice were exposed to the UVA sources 30 min/day 5 days/week, in equal erythemogenic doses, calculated by using the Commission Internationale de l'Eclairage human erythema action spectrum. Equal erythemogenic doses of TL 09 and UVASUN induced the same degree of skin pigmentation, but skin tumor development was enhanced in mice exposed to TL 09 compared with UVASUN (P < 0.0005). For all but one tumor, endpoint pretreatment with TL 09 or UVASUN for 91 days did not influence tumor development during subsequent exposure to SOLAR UV radiation 10 min/day, 4 days/week. Exposure to the two UVA radiation sources after 91 days of SOLAR UV exposure significantly enhanced skin tumor development. Overall, the data on the interaction between exposure to the UVA sources and SOLAR UV indicated that the risk of SOLAR UV-induced carcinogenesis was independent of the type of prior-UVA exposure and post-UVA exposure.
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PMID:Carcinogenic and melanogenic effects of a filtered metal halide UVA source and a tubular fluorescent UVA tanning source with or without additional solar-simulated UV radiation in hairless mice. 748 Jan 54


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