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[PMID]:28985619
[Au] Autor:Abbo BG; Hulslander LE; Goldade DA
[Ad] Endereço:U.S. Department of Agriculture, Animal and Plant Health Inspection Service, National Wildlife Research Center, Fort Collins, CO, 80521, USA. Electronic address: Benjamin.Abbo@aphis.usda.gov.
[Ti] Título:Determination of 20, 25-diazacholesterol in avian matrices by high performance liquid chromatography/tandem mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1065-1066:129-133, 2017 Oct 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Wildlife contraceptives are an emerging tool for minimizing human-wildlife conflicts. One promising avian contraceptive compound, 20,25-diazacholesterol (DAC), reduces fertility by inhibiting cholesterol synthesis. A reliable analytical method for DAC was required in support of its registration for use as a reproductive control agent in pest bird species. A liquid chromatographic method employing tandem mass spectrometry (LC-MS/MS) was developed for the analysis of tissue extracts following solid phase extraction clean-up. Tissues analyzed were whole body samples from crows, monk parakeets, and quails and liver samples from crows and quails. Excellent sensitivity and selectivity was afforded by tandem mass spectrometry. The method accuracy of DAC from various tissue samples fortified at parts-per-million (ppm) and parts-per-billion (ppb) concentrations was high (>90%) with excellent precision (<10% relative standard deviation). Lower limits of detection were excellent in all tissues types, ranging from 1 to 11ppb in whole body matrices and 9.9-34ppb in liver matrices.
[Mh] Termos MeSH primário: Azacosterol/análise
Aves
Cromatografia Líquida de Alta Pressão/métodos
Anticoncepcionais/análise
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Limite de Detecção
Modelos Lineares
Fígado/química
Controle de Pragas
Reprodutibilidade dos Testes
Extração em Fase Sólida/métodos
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contraceptive Agents); EPT876J73A (Azacosterol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


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[PMID]:22182332
[Au] Autor:Yoder CA; Mayle BA; Furcolow CA; Cowan DP; Fagerstone KA
[Ad] Endereço:National Wildlife Research Center, Fort Collins, Colorado, USA. cyoder303@gmail.com
[Ti] Título:Feeding of grey squirrels (Sciurus carolinensis) with the contraceptive agent DiazaCon™: effect on cholesterol, hematology, and blood chemistry.
[So] Source:Integr Zool;6(4):409-19, 2011 Dec.
[Is] ISSN:1749-4877
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Grey squirrels (Sciurus carolinensis) are an invasive species in Britain and Italy. They have replaced native red squirrels (Sciurus vulgaris) throughout most of Britain, and cause damage to trees. Currently, lethal control is used to manage grey squirrel populations in Britain, but nonlethal methods might be more acceptable to the public. One such method is contraception with 20,25-diazacholesterol dihydrochloride (DiazaCon™). DiazaCon™ inhibits the conversion of desmosterol to cholesterol, resulting in increasing desmosterol concentrations and decreasing cholesterol concentrations. Because cholesterol is needed for the synthesis of steroid reproductive hormones, such as progesterone and testosterone, inhibition of cholesterol synthesis indirectly inhibits reproduction. Desmosterol is used as a marker of efficacy in laboratory studies with species that do not reproduce readily in captivity. Grey squirrels were gavaged with a DiazaCon™ solution for 2 days, and then fed DiazaCon™-coated peanuts for an additional 8 days at target doses of 50 and 100 mg DiazaCon™ per kg body weight. There was a significant difference in cholesterol concentrations in the treatment groups compared to the control group. Cholesterol was reduced by ≥ 40% for 2 months in both treatment groups. There were no differences among groups with respect to blood chemistry and hematology parameters, and mean values are reported. The mean overall dose of DiazaCon™ received was 29.0 ± 1.6 and 55.3 ± 4.3 mg/kg in the low (50 mg/kg) and high dose (100 mg/kg) groups, respectively. DiazaCon™ might provide an effective, acceptable alternative to lethal control.
[Mh] Termos MeSH primário: Azacosterol/farmacologia
Colesterol/sangue
Anticoncepcionais/farmacologia
Desmosterol/metabolismo
Espécies Introduzidas
Sciuridae/fisiologia
[Mh] Termos MeSH secundário: Animais
Azacosterol/administração & dosagem
Análise Química do Sangue/veterinária
Anticoncepcionais/administração & dosagem
Desmosterol/sangue
Relação Dose-Resposta a Droga
Inglaterra
Testes Hematológicos/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contraceptive Agents); 313-04-2 (Desmosterol); 97C5T2UQ7J (Cholesterol); EPT876J73A (Azacosterol)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:111220
[Lr] Data última revisão:
111220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111221
[St] Status:MEDLINE
[do] DOI:10.1111/j.1749-4877.2011.00247.x


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[PMID]:14979575
[Au] Autor:Yoder CA; Andelt WF; Miller LA; Johnston JJ; Goodall MJ
[Ad] Endereço:National Wildlife Research Center, 4101 Laporte Avenue, Fort Collins, Colorado 80521-2154, USA. christi.yoder@usda.gov
[Ti] Título:Effectiveness of twenty, twenty-five diazacholesterol, avian gonadotropin-releasing hormone, and chicken riboflavin carrier protein for inhibiting reproduction in Coturnix quail.
[So] Source:Poult Sci;83(2):234-44, 2004 Feb.
[Is] ISSN:0032-5791
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Contraception may provide a useful nonlethal management tool when it is desirable to reduce populations of birds. We tested the efficacy of 20,25 diazacholesterol, and immunization with avian gonadotropin-releasing hormone (AGnRH-I) and chicken riboflavin carrier protein (cRCP) as contraceptives and investigated their modes of action in Coturnix quail (Coturnix coturnix japonica). Females that were paired with males treated with 20,25 diazacholesterol produced lower percentages of eggs that were fertile and hatched. Females treated with 20,25 diazacholesterol and paired with control males laid fewer eggs, and lower percentages of their eggs were fertile and hatched. Treatment with 20,25 diazacholesterol reduced testosterone levels in males and progesterone levels in females. Nonesterified cholesterol levels were reduced, whereas desmosterol levels increased in birds treated with 20,25 diazacholesterol. Treatment with AGnRH-I and cRCP immunocontraceptive vaccines did not decrease average egg production and hatchability or hormone levels, but this failure might have been due to the vaccination protocol. If registered, wildlife managers may be able to use 20,25 diazacholesterol when other methods, such as lethal control, are undesirable for reducing damage caused by specific breeding behaviors such as the building of nests.
[Mh] Termos MeSH primário: Azacosterol/farmacologia
Proteínas de Transporte/farmacologia
Coturnix/fisiologia
Fertilidade/efeitos dos fármacos
Hormônio Liberador de Gonadotropina/farmacologia
Proteínas de Membrana Transportadoras
Oviposição/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Colesterol/sangue
Anticoncepcionais/farmacologia
Coturnix/sangue
Desmosterol/sangue
Feminino
Masculino
Progesterona/sangue
Riboflavina/metabolismo
Testosterona/sangue
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Carrier Proteins); 0 (Contraceptive Agents); 0 (Membrane Transport Proteins); 0 (riboflavin-binding protein); 313-04-2 (Desmosterol); 33515-09-2 (Gonadotropin-Releasing Hormone); 3XMK78S47O (Testosterone); 4G7DS2Q64Y (Progesterone); 97C5T2UQ7J (Cholesterol); EPT876J73A (Azacosterol); TLM2976OFR (Riboflavin)
[Em] Mês de entrada:0407
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040226
[St] Status:MEDLINE


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[PMID]:12507656
[Au] Autor:Singh SK; Chakravarty S
[Ad] Endereço:Department of Zoology, Banaras Hindu University, Varanasi 221005, India. shioks@banaras.ernet.in
[Ti] Título:Antispermatogenic and antifertility effects of 20,25-diazacholesterol dihydrochloride in mice.
[So] Source:Reprod Toxicol;17(1):37-44, 2003 Jan-Feb.
[Is] ISSN:0890-6238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The effect of intraperitoneal administration for 28 days of 10, 20, and 30 mg/kg body weight per day of 20,25-diazacholesterol dihydrochloride (SC 12937), a hypocholesterolemic agent, on the testis of Parkes (P) strain mice was investigated. Histologically, testes in mice treated with 10 or 20 mg/kg body weight of SC 12937 showed non-uniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; the affected tubules showed intraepithelial vacuolation, occurrence of giant cells, exfoliation of germ cells, and marginal condensation of chromatin in round spermatids. In both dosage groups, only 11-12% of the seminiferous tubules were affected, and no significant differences were found in the frequency of affected tubules between the two groups. By contrast, testes in mice treated with 30 mg/kg body weight of the drug exhibited a degenerated appearance of germ cells in all seminiferous tubules. The treatment also had adverse effects on motility, viability, morphology, and number of spermatozoa in the cauda epididymidis, and on fertility. Even 56 days after drug withdrawal, the above parameters remained markedly affected. Our results thus suggest that SC 12937 treatment causes antispermatogenic and antifertility effects in P mice and that the effects are not reversible up to 56 days after drug withdrawal. This compound may prove useful in the control of rodent populations.
[Mh] Termos MeSH primário: Anticolesterolemiantes/toxicidade
Azacosterol/toxicidade
Esterilizantes Químicos/toxicidade
Fertilidade/efeitos dos fármacos
Espermatogênese/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/administração & dosagem
Azacosterol/administração & dosagem
Esterilizantes Químicos/administração & dosagem
Relação Dose-Resposta a Droga
Injeções Intraperitoneais
Masculino
Camundongos
Camundongos Endogâmicos
Modelos Animais
Epitélio Seminífero/efeitos dos fármacos
Epitélio Seminífero/patologia
Motilidade Espermática/efeitos dos fármacos
Espermatozoides/efeitos dos fármacos
Espermatozoides/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Chemosterilants); EPT876J73A (Azacosterol)
[Em] Mês de entrada:0306
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:030101
[St] Status:MEDLINE


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[PMID]:12502398
[Au] Autor:Johnston JJ; Goodall MJ; Yoder CA; Furcolow CA; Goldade DA; Kimball BA; Miller LA
[Ad] Endereço:United States Department of Agriculture, National Wildlife Research Center, 4101 LaPorte Avenue, Fort Collins, Colorado 80521, USA. john.johnston@usda.gov
[Ti] Título:Desmosterol: a biomarker for the efficient development of 20,25-diazacholesterol as a contraceptive for pest wildlife.
[So] Source:J Agric Food Chem;51(1):140-5, 2003 Jan 01.
[Is] ISSN:0021-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:20,25-Diazacholesterol is being evaluated as a contraceptive for the nonlethal control of avian and mammalian wildlife pests. The identification of an analyte in blood which was highly correlated with absorbed dose and efficacy is valuable for determining effective formulations and dosing variables. Such an analyte or biomarker is also valuable for determining the percentage of pest populations that consume an effective dose of the active ingredient in the field. HPLC analyses of blood collected from dosed animals failed to detect 20,25-diazacholesterol but indicated that levels of free cholesterol and related compounds were affected by 20,25-diazacholesterol absorption. The greatest percent change in chromatographic peak area associated with 20,25-diazacholesterol administration was observed for desmosterol, a cholesterol precursor. 20,25-Diazacholesterol appeared to block the conversion of desmosterol to cholesterol, resulting in an elevated concentration of the precursor. The elevation of blood desmosterol levels is being used as an indicator of 20,25-diazacholesterol absorption and to facilitate the development of a 20,25-diazacholesterol-based contraceptive for pest wildlife.
[Mh] Termos MeSH primário: Azacosterol/administração & dosagem
Biomarcadores/sangue
Anticoncepcionais/administração & dosagem
Coturnix/sangue
Cervos/sangue
Desmosterol/sangue
Controle de Pragas
[Mh] Termos MeSH secundário: Animais
Azacosterol/farmacocinética
Cromatografia Líquida de Alta Pressão
Anticoncepcionais/farmacocinética
Feminino
Cromatografia Gasosa-Espectrometria de Massas
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Contraceptive Agents); 313-04-2 (Desmosterol); EPT876J73A (Azacosterol)
[Em] Mês de entrada:0302
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:021228
[St] Status:MEDLINE


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[PMID]:11417624
[Au] Autor:Johnston JJ; Goodall MJ; Hurley JC; Yoder CA; Miller LA
[Ad] Endereço:USDA/APHIS/WS/National Wildlife Research Center, Analytical Chemistry Project, Fort Collins, CO 80521, USA.
[Ti] Título:Determination of DiazaCon in quail feed and quail serum by ion pair reversed-phase chromatography.
[So] Source:J AOAC Int;84(3):634-9, 2001 May-Jun.
[Is] ISSN:1060-3271
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Liquid chromatographic (LC) methods were developed for quantitating the potential avian contraceptive DiazaCon in quail feed and serum. DiazaCon was extracted from ground quail feed with basic n-butyl chloride. The n-butyl chloride extract was evaporated to dryness. The DiazaCon residues were dissolved in an aqueous methanolic ion pairing solution and quantitated by LC at 206 nm. Avian sera was combined with an equal volume of a pH 4 aqueous solution of ion pairing reagent and filtered to remove interfering proteins. DiazaCon was quantitated by LC. Mean recoveries for 500 and 2000 ppm fortified feed were 89.1 and 91.0%, respectively. The mean recovery for sera fortified at 5 levels ranging from 35 to 2000 ppm was 84.9%. Method limits of detection were approximately 14 and 13 ppm for feed and sera, respectively.
[Mh] Termos MeSH primário: Ração Animal/análise
Azacosterol/análise
Cromatografia Líquida de Alta Pressão/métodos
Anticoncepcionais/análise
Coturnix/sangue
[Mh] Termos MeSH secundário: Animais
Azacosterol/sangue
Azacosterol/química
Anticoncepcionais/sangue
Concentração de Íons de Hidrogênio
Indicadores e Reagentes
Espectroscopia de Ressonância Magnética
Espectrometria de Massas
Estrutura Molecular
Controle de Qualidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contraceptive Agents); 0 (Indicators and Reagents); EPT876J73A (Azacosterol)
[Em] Mês de entrada:0112
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:010622
[St] Status:MEDLINE


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[PMID]:11377165
[Au] Autor:Xie W; Peng H; Kim DI; Kunkel M; Powis G; Zalkow LH
[Ad] Endereço:School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.
[Ti] Título:Structure-activity relationship of aza-steroids as PI-PLC inhibitors.
[So] Source:Bioorg Med Chem;9(5):1073-83, 2001 May.
[Is] ISSN:0968-0896
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3beta-hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC(50) values of 7.4 and 7.5 microM, respectively. The 20alpha epimer, 8a2 (IC(50)=0.64 microM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20beta epimer, 8a1 (IC(50)=32.2 microM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC(50)=19.7 microM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC(50)=7.4 microM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC(50)=17.4 microM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors.(3) However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI(50) value (MG-MID) of 5.75 microM for 54 tumors.
[Mh] Termos MeSH primário: Azacosterol/síntese química
Azacosterol/farmacologia
Azasteroides/síntese química
Azasteroides/farmacologia
Colestanóis/síntese química
Colestanóis/farmacologia
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/farmacologia
Fosfolipases Tipo C/antagonistas & inibidores
[Mh] Termos MeSH secundário: Ensaios de Seleção de Medicamentos Antitumorais/métodos
Seres Humanos
Concentração Inibidora 50
Fosfatidilinositol Diacilglicerol-Liase
Fosfoinositídeo Fosfolipase C
Relação Estrutura-Atividade
Células Tumorais Cultivadas/citologia
Células Tumorais Cultivadas/efeitos dos fármacos
Fosfolipases Tipo C/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Azasteroids); 0 (Cholestanols); 0 (Enzyme Inhibitors); 2278-46-8 (22,25-diazacholestanol); EC 3.1.4.- (Type C Phospholipases); EC 3.1.4.11 (Phosphoinositide Phospholipase C); EC 4.6.1.13 (Phosphatidylinositol Diacylglycerol-Lyase); EPT876J73A (Azacosterol)
[Em] Mês de entrada:0110
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:010530
[St] Status:MEDLINE


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[PMID]:8491258
[Au] Autor:Morales-Aguilera A; Sampayo-Reyes A
[Ad] Endereço:División de Farmacología, Unidad de Investigación Biomédica del Noreste, Monterrey, N.L., Mexico.
[Ti] Título:Molecular changes in erythrocyte membranes induced by long-term administration of clofibrate.
[So] Source:Eur J Pharmacol;245(2):89-95, 1993 Apr 15.
[Is] ISSN:0014-2999
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:It has been reported that an enantiomer ((S)-(-)-4) of clofibric acid, and the racemate, can block the chloride conductance of skeletal muscle membrane. It has also been reported that several analogs of clofibric acid inhibit the HCO3(-)-Cl- exchange of erythrocytes. Since the two effects are probably similar biophysical membrane phenomena, the possibility of a common molecular mechanism arises. We exposed Sprague-Dawley male rats to long-term administration of clofibrate and 20,25-diazacholesterol (20,25-D) for comparison, at equipotent doses. Clofibrate (but not 20,25-diazacholesterol) produced a significant increase in density of the 220,000 Da band (beta-spectrin) and a decrease, also significant, in density of bands 2.1, 2.2, 2.3, 2.6 (syndeins or ankyrins) and of bands 4.1 and 6. Thus, clofibrate exhibits a manifold effect on the protein profile of the erythrocyte membrane cytoskeleton which, due to the lack of effect of 20-25-D, does not seem to be produced by the hypolipidemic effect per se, and thus deserves further study.
[Mh] Termos MeSH primário: Clofibrato/farmacologia
Membrana Eritrocítica/metabolismo
[Mh] Termos MeSH secundário: Animais
Azacosterol/farmacologia
Proteínas Sanguíneas/metabolismo
Colesterol/sangue
Citoesqueleto/efeitos dos fármacos
Densitometria
Membrana Eritrocítica/efeitos dos fármacos
Membrana Eritrocítica/ultraestrutura
Indicadores e Reagentes
Masculino
Microscopia Eletrônica de Varredura
Fragilidade Osmótica/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Proteins); 0 (Indicators and Reagents); 97C5T2UQ7J (Cholesterol); EPT876J73A (Azacosterol); HPN91K7FU3 (Clofibrate)
[Em] Mês de entrada:9306
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:930415
[St] Status:MEDLINE


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[PMID]:2205410
[Au] Autor:Tanimoto Y; Fukao K; Yoshiga K; Takada K; Ohyama Y; Okuda K
[Ad] Endereço:Department of Oral and Maxillofacial Surgery I, Hiroshima University, School of Dentistry, Japan.
[Ti] Título:Effect of chemical carcinogens on cholesterol biosynthetic pathways in the skin of mice.
[So] Source:Carcinogenesis;11(9):1647-51, 1990 Sep.
[Is] ISSN:0143-3334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The metabolism of zymosterol and mevalonic acid was studied in vitro using the skin homogenates of 3-methylcholanthrene (3MC), diazacholesterol-treated and untreated mice. In normal mouse skin only lathosterol was a major metabolite and the other metabolites, cholesta-5,7,24-trien-3 beta-ol, desmosterol, cholesterol and 7-dehydrocholesterol were much less abundant. However, in the skin homogenate of mice treated with 3MC lathosterol production was depressed, while the production of cholesta-5,7,24-trien-3 beta-ol and desmosterol was significantly increased, the cholesterol level being normal or a little higher. In contrast, in the skin homogenate of mice administered diazacholesterol the production of both lathosterol and cholesterol was almost completely blocked with the slightly increased production of cholesta-5,7,24-trien-3 beta-ol and desmosterol. The metabolism in vitro of [2-14C]-mevalonic acid was quite similar to that of zymosterol, and no additional product which might possibly have been produced by the Kandutsch-Russell pathway was observed. Two pathways for cholesterol biosynthesis, therefore, may exist in mouse skin; the first is lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----lathosterol----7-dehydrocholesterol----cholesterol, and the second by Bloch: lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----cholesta-5,7,24-trien-3 beta-ol----desmosterol----cholesterol. When mouse skin is treated with 3-MC the former pathway is virtually blocked and the latter is stimulated, keeping the level of cholesterol in the tissue constant or a little higher than normal, which seems to be a significant change in the early stage of chemical carcinogenesis.
[Mh] Termos MeSH primário: Azacosterol/farmacologia
Carcinógenos/farmacologia
Colesterol/análogos & derivados
Colesterol/biossíntese
Metilcolantreno/farmacologia
Ácido Mevalônico/metabolismo
Pele/metabolismo
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos
Camundongos Endogâmicos ICR
Técnica de Diluição de Radioisótopos
Valores de Referência
Pele/efeitos dos fármacos
Esteróis/metabolismo
Trítio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinogens); 0 (Sterols); 10028-17-8 (Tritium); 56-49-5 (Methylcholanthrene); 97C5T2UQ7J (Cholesterol); EPT876J73A (Azacosterol); PU2755PT4O (zymosterol); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:9010
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:900901
[St] Status:MEDLINE


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[PMID]:3356016
[Au] Autor:Fukao K; Tanimoto Y; Kayata Y; Yoshiga K; Takada K; Ohyama Y; Okuda K
[Ad] Endereço:Department of Oral and Maxillofacial Surgery I, Hiroshima University, School of Dentistry, Japan.
[Ti] Título:Alteration of cholesterol biosynthetic pathways in the skin of mice administered polycyclic aromatic hydrocarbons.
[So] Source:Cancer Res;48(9):2555-60, 1988 May 01.
[Is] ISSN:0008-5472
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:When polycyclic aromatic hydrocarbons were applied solely or together with a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) to the skin of mice, a marked decrease in the level of lathosterol was observed, reflecting a significant change in the metabolism of sterols. Yet the total amount of cholesterol was not changed. When diazacholesterol (a metabolic inhibitor) was administered to mice, both desmosterol and 5 alpha-cholesta-7,24-dien-3 beta-ol accumulated in the skin, whereas the level of lathosterol decreased. These results seem to suggest that a significant portion of lathosterol is formed via 5 alpha-cholesta-7,24-dien-3 beta-ol in addition to the pathway through methostenol. When polycyclic aromatic hydrocarbon was applied to the skin of the mouse treated with diazacholesterol, a significant increase of desmosterol and a marked drop of the level of 5 alpha-cholesta-7,24-dien-3 beta-ol were observed. These results strongly suggest that polycyclic aromatic hydrocarbons perturb the metabolism of sterol in the skin of mice while keeping the total amount of cholesterol unchanged. A similar metabolism also seems to be operating in tumor tissue itself.
[Mh] Termos MeSH primário: Carcinógenos/farmacologia
Colesterol/biossíntese
Compostos Policíclicos/farmacologia
Pele/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Azacosterol/farmacologia
Masculino
Espectrometria de Massas
Metilcolantreno/farmacologia
Camundongos
Pele/metabolismo
Neoplasias Cutâneas/análise
Esteróis/análise
Acetato de Tetradecanoilforbol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carcinogens); 0 (Polycyclic Compounds); 0 (Sterols); 56-49-5 (Methylcholanthrene); 97C5T2UQ7J (Cholesterol); EPT876J73A (Azacosterol); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[Em] Mês de entrada:8805
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:880501
[St] Status:MEDLINE



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