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)

The tumor-producing and skin-irritating activity of the antipsoriatic drug dithranol and its 10-acyl analogues butantrone (10-butyryl dithranol), 10-isobutyryl dithranol and 10-valeryl dithranol were studied in 650 SENCAR mice using a two-stage skin carcinogenesis assay. An initiation with 20 micrograms of 7,12-dimethylbenz(alpha)anthracene (DMBA) was followed 2 weeks later by three applications per week of the test compounds in 50 microliter of acetone for 21 weeks. In addition the compounds were studied without DMBA pre-treatment using application periods of 21 and 36 weeks. The concentration of dithranol was the maximum tolerated, 3.5 mM. For the less irritating 10-acyl analogues 30 mM solutions were used. The first signs of skin irritation were observed after an application period of 1-2 weeks and the irritation continued to the end of the experiment in all groups except the acetone controls. Dithranol caused the most severe irritation although the differences between the groups were not pronounced. On histopathology, the majority of animals had hyperplasia and other inflammatory changes of the skin. The first papillomas appeared 8-11 weeks after initiation and the incidences of papillomas at the end of the experiment were 85% (dithranol 3.5 mM), 16% (butantrone 30 mM), 36% (10-isobutyryl dithranol 30 mM) and 50% (10-valeryl dithranol 30 mM). Without initiation the incidences were 6 and 2% (dithranol), 2 and 2% (butantrone) and 2 and 0% (10-valeryl dithranol) in the 21- and 36-week studies, respectively. Histologically, the papillomas were mostly squamous papillomas and only a few keratoacanthomas were found. It is concluded that the tumor-producing and skin-irritating activity of dithranol is clearly greater than that of butantrone, 10-isobutyryl dithranol and 10-valeryl dithranol.
Carcinogenesis 1986 Oct
PMID:Tumor-producing and skin-irritating activity of dithranol (anthralin) and its 10-acyl analogues in SENCAR mice. 375 76

Previous studies had indicated that complete skin tumor promoters of the phorbol ester class induce epidermal transglutaminase and cornification in a subpopulation of cultured mouse epidermal basal cells in proportion to their promoting properties. This report describes the effect of promoting agents other than phorbol esters on the differentiation response and explores the pharmacological basis for the heterogeneity of responsiveness among subpopulations. The potent indole alkaloid skin tumor promoter, teleocidin, induces transglutaminase to the same extent or greater than 12-O-tetradecanoylphorbol-13-acetate (TPA). The highly inflammatory and cytotoxic non-promoting agent resiniferotoxin is not an inducer of transglutaminase. Incomplete skin tumor promoters, mezerein and retinyl phorbol acetate, were as potent as TPA as inducers of transglutaminase. Anthralin and benzoyl peroxide, skin tumor promoters which do not bind to the phorbol ester receptor, do not induce transglutaminase. TPA was used to study the influence of the state of epidermal maturation at the time of exposure on the differentiation response. Epidermal basal cells were induced to differentiate by elevating extracellular calcium to 1.2 mM. TPA markedly accelerates the differentiation program when given simultaneous with exposure to 1.2 mM Ca2+ as indicated by measurements of DNA synthesis, transglutaminase activity and cornified cells. Furthermore, epidermal cells committed to differentiate by switching to 1.2 mM Ca2+ medium remain responsive to the differentiative effects of TPA for at least 5 h. These results indicate that the induction of transglutaminase activity and cornification in epidermal basal cells is characteristic of phorbol ester promoters or other agents that bind to the phorbol ester receptor but is not characteristic of all skin tumor promoters. This result suggests that the phorbol ester receptor regulates epidermal differentiation. The state of differentiation of epidermal cells at the time of phorbol ester exposure may determine whether the cellular response will be in a proliferative or differentiative pathway.
Carcinogenesis 1983 Nov
PMID:The induction of epidermal transglutaminase and terminal differentiation by tumor promoters in cultured epidermal cells. 613 80

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H2O2 cytotoxicity.
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PMID:Does manganese protect cultured human skin fibroblasts against oxidative injury by UVA, dithranol and hydrogen peroxide? 749 40