Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Science ; 166(3909): 1158-9, 1969 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-5348286

RESUMO

Dialkyl ethers of diols (dialkoxyalkanes), naturally occurring lipids, have been isolated from the jaw oil of the porpoise Phocoena phocoena. The principal constituents are dialkoxypentanes containing two 18-carbon chains. The alkoxy linkage may play an important role in the metabolism of the diol lipids.


Assuntos
Glicóis/isolamento & purificação , Óleos/análise , Animais , Cromatografia em Camada Fina , Golfinhos , Glicóis/análise , Arcada Osseodentária/análise
2.
Science ; 176(4037): 926-8, 1972 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-5033637

RESUMO

More than two-thirds of the triacylglycerols from the acoustic tissues of the porpoise (Tursiops gilli) consist of 2 moles of isovaleric acid for every 1 mole of long-chain acids. Cranial blubber, which has no distinct acoustic function, does not contain these unusual glycerides. The presence of large amounts of diisovaleroylisopentadecanoylglycerol suggests that this structure may be particularly important in sound transmission through lipid-protein matrices.


Assuntos
Acústica , Golfinhos/metabolismo , Glicerídeos/análise , Órgãos dos Sentidos/análise , Valeratos/análise , Animais , Cromatografia Gasosa , Cromatografia em Camada Fina , Golfinhos/fisiologia
3.
Mol Cell Biol ; 11(6): 3307-16, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2038333

RESUMO

Mutations of yeast CYC8 or TUP1 genes greatly reduce the degree of glucose repression of many genes and affect other regulatory pathways, including mating type. The predicted CYC8 protein contains 10 copies of the 34-amino-acid tetratricopeptide repeat unit, and the predicted TUP1 protein has six repeated regions found in the beta subunit of heterotrimeric G proteins. The absence of DNA-binding motifs and the presence of these repeated domains suggest that the CYC8 and TUP1 proteins function via protein-protein interaction with transcriptional regulatory proteins. We raised polyclonal antibodies against TrpE-CYC8 and TrpE-TUP1 fusion proteins expressed in Escherichia coli. The CYC8 and TUP1 proteins from yeast cells were detected as closely spaced doublets on Western immunoblots of sodium dodecyl sulfate-polyacrylamide gels. Western blots of nondenaturing gels revealed that both proteins are associated in a high-molecular-weight complex with an apparent size of 1,200 kDa. In extracts from delta cyc8 strains, the size of the complex is reduced to 830 kDa. The CYC8 and TUP1 proteins were coprecipitated by either antiserum, further supporting the conclusion that they are associated with each other. The complex could be reconstituted in vitro by mixing extracts from strains with complementary mutations in the CYC8 and TUP1 genes.


Assuntos
Proteínas de Ligação a DNA , Proteínas Fúngicas/genética , Genes Fúngicos , Genes Fúngicos Tipo Acasalamento , Glucose/metabolismo , Proteínas Nucleares , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Western Blotting , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Proteínas Fúngicas/isolamento & purificação , Proteínas Fúngicas/metabolismo , Genótipo , Substâncias Macromoleculares , Peso Molecular , Plasmídeos , Saccharomyces cerevisiae/genética
4.
Mol Cell Biol ; 16(12): 6707-14, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8943325

RESUMO

The Cyc8 (Ssn6)-Tup1 corepressor complex is required for repression in several important regulatory systems in yeast cells, including glucose repression and mating type. Cyc8-Tup1 is recruited to target genes by interaction with diverse repressor proteins that bind directly to DNA. Since the complex has a large apparent molecular mass of 1,200 kDa on nondenaturing gels (F. E. Williams, U. Varanasi, and R. J. Trumbly, Mol. Cell. Biol. 11:3307-3316, 1991), we used a variety of approaches to determine its actual subunit composition. Immunoprecipitation of epitope-tagged complex and reconstitution of the complex from in vitro-translated proteins demonstrated that only the Cyc8 and Tup1 proteins were present in the complex. Hydrodynamic properties showed that these proteins have unusually large Stokes radii, low sedimentation coefficients, and high frictional ratios, all characteristic of asymmetry which partly accounts for the apparent high molecular weight. Calculation of native molecular weights from these properties indicated that the Cyc8-Tup1 complex is composed of one Cyc8 subunit and four Tup1 subunits. This composition was confirmed by reconstitution of the complex from Cyc8 and Tup1 expressed in vitro and analysis by one- and two-dimensional gel electrophoresis.


Assuntos
Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Proteínas Nucleares , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Sequência de Bases , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/metabolismo , Dados de Sequência Molecular
5.
Cancer Res ; 49(5): 1171-7, 1989 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-2917348

RESUMO

The 1-butanol adduct enhancement version of the 32P-postlabeling assay was used to measure the levels of hepatic DNA adducts in the marine flatfish, English sole (Parophrys vetulus), sampled from the Duwamish Waterway and Eagle Harbor, Puget Sound, WA, where they are exposed to high concentrations of sediment-associated chemical contaminants and exhibit an elevated prevalence of hepatic neoplasms. Hepatic DNA was also analyzed from English sole from a reference area (Useless Bay, WA) and from reference English sole treated with organic-solvent extracts of sediments from the two contaminated sites. Autoradiograms of thin-layer chromatograms of 32P-labeled hepatic DNA digests from English sole from the contaminated sites exhibited up to three diagonal radioactive zones, which were not present in autoradiograms of thin-layer chromatogram maps of 32P-labeled DNA digests from English sole from the reference site. These diagonal radioactive zones contained several distinct spots as well as what appeared to be multiple overlapping adduct spots. The levels (nmol of adducts/mol of nucleotides) of total DNA adducts for English sole from Duwamish Waterway and Eagle Harbor were 26 +/- 28 (DS) and 17 +/- 9.6, respectively. All autoradiograms of DNA from fish from the contaminated sites exhibited a diagonal radioactive zone where DNA adducts of chrysene, benzo(a)pyrene, and dibenz(a,h)anthracene, formed in vitro using English sole hepatic microsomes, were shown to chromatograph. English sole treated with extracts of the contaminated sediments had adduct profiles generally similar to those for English sole from the respective contaminated sites. The chromatographic characteristics of the adducts and the similarities in adduct profiles between field-sampled English sole and those treated with contaminated sediment extracts suggested that hydrophobic aromatic compounds of anthropogenic origin were adducted to hepatic DNA of sole from contaminated sites, but not in sole from the reference site. Moreover, an initial study with winter flounder (Pseudopleuronectes americanus) from Boston Harbor, MA, an area where high concentrations of sediment-associated chemicals are present, revealed a pattern of hepatic DNA-adducts (9.0 +/- 7.8 nmol of adducts/mol of nucleotides) similar to that observed for English sole from Eagle Harbor.


Assuntos
DNA/metabolismo , Linguados/metabolismo , Linguado/metabolismo , Fígado/análise , Compostos Policíclicos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes da Água/metabolismo , Animais , Autorradiografia
6.
Cancer Res ; 46(8): 3817-24, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3731058

RESUMO

Metabolism of benzo(a)pyrene (BaP) in vivo and in vitro was studied using two benthic fish species, English sole (Parophrys vetulus) and starry flounder (Platichthys stellatus), and Sprague-Dawley rats. At 24 h after administration of BaP (7.9 mumol/kg of body weight) to fish either p.o. (Experiment 1) or i.p. (Experiment 2), the specific activity of binding of BaP metabolites to hepatic DNA (pmol of BaP equivalent per mg of DNA) was higher in sole [2.1 in Experiment 1; 28 +/- 5 (SE) in Experiment 2] than in flounder (0.5 in Experiment 1; 14 +/- 4 in Experiment 2). Treatment of bile with beta-glucuronidase and arylsulfatase released a significantly higher proportion of 7,8-dihydroxy-7,8-dihydro-BaP (BaP 7,8-diol) from sole bile than from flounder bile in both experiments. However, the rate of BaP metabolism and rate of formation of BaP 7,8-diol by hepatic microsomes were comparable for both fish species. Thus, the differences in both the level of DNA binding and the concentration of BaP 7,8-diol in bile of BaP-exposed sole and flounder were apparently due to differences in detoxication, rather than formation, of BaP 7,8-oxide and BaP 7,8-diol-9,10-epoxide. The rate of formation of BaP 7,8-diol by rat liver microsomes (28 +/- 1 pmol of BaP 7,8-diol formed per min per mg of protein) was comparable to that by hepatic microsomes from both fish species (50 +/- 10 for sole and 33 +/- 6 for flounder), although the rate of BaP metabolism (600 +/- 200) was approximately 3 times greater than that by the fish species (190 +/- 60 for sole and 180 +/- 40 for flounder). Thus, greater proportion of BaP was converted to BaP 7,8-diol by liver microsomes of fish species than rat. These differences in BaP metabolism in vitro help explain, in part, the substantially lower binding (0.3 +/- 0.1; Experiment 2) for hepatic DNA in BaP-exposed rat than that in either sole or flounder.


Assuntos
Benzo(a)pireno/metabolismo , DNA/metabolismo , Di-Hidroxi-Di-Hidrobenzopirenos , Peixes/metabolismo , Fígado/metabolismo , Animais , Benzopirenos/metabolismo , Bile/metabolismo , Cromatografia Líquida de Alta Pressão , Glutationa/metabolismo , Glutationa Transferase/análise , Neoplasias Hepáticas Experimentais/induzido quimicamente , Ratos , Ratos Endogâmicos , Especificidade da Espécie
7.
Biochim Biophys Acta ; 409(3): 304-10, 1975 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-1203247

RESUMO

The whole brain of a porpoise (Delphinus delphis) comprised 23.1 wt% of phospholipids on a dry weight basis. Ethanolamine phosphoglycerides (36.6 wt%), choline phosphoglycerides (27.3 wt%), and serine phosphoglycerides (16.9 wt%) were the major components of the phospholipids. A unique feature of the data was the occurrence of large amounts of isovaleric acid in choline phosphoglucerides (28.1 mol%) and ethanolamine phosphoglycerides (6.4 mol%), together with 11.6 and 15.2 mol% of long-chain (C11--C16) iso-acids, respectively. Interestingly, serine phosphoglycerides did not contain detectable amounts of isovaleric acid although trace amounts of long-chain iso-acids were present. No previous evidence exists to show that appreciable amounts of a short-chain acid can be accommodated in animal phospholipids. The occurrence of isovaleric acid in the principal phosphoglycerides of the porpoise brain elicits an interest in how such an anomalous structure is accommodated in the lipid bilayers of the neural membranes.


Assuntos
Encéfalo/metabolismo , Golfinhos/metabolismo , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos , Animais , Cerebrosídeos/metabolismo , Colesterol/metabolismo , Membranas/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositóis/metabolismo , Fosfatidilserinas/metabolismo , Esfingomielinas/metabolismo , Valeratos/metabolismo
8.
Am J Med ; 66(1): 163-71, 1979 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-369373

RESUMO

Two male patients with Goodpasture's syndrome manifesting as severe pulmonary hemorrhage with minimal renal abnormalities are described. Both patients had microscopic hematuria with normal renal function, and one had transient proteinuria. Renal glomerular histology was normal and electron microscopic findings revealed no electron-dense deposits, but immunofluorescence of immunoglobulin G (IgG) was positive in a linear fashion along glomerular capillary basement membranes in both patients. Pulmonary hemorrhage was arrested following prednisone therapy, and both patients have normal pulmonary and renal function at five and 13 months of follow-up. The literature on patients with Goodpasture's syndrome, pulmonary hemorrhage and normal renal function with minimal proteinuria is reviewed. It is suggested that a subset of patients with Goodpasture's syndrome have pulmonary hemorrhage as their major manifestation. Since prednisone seems to have an apparent beneficial effect on pulmonary hemorrhage, and relatively good prognosis, this diagnosis should be considered in patients with idiopathic pulmonary hemorrhage.


Assuntos
Doença Antimembrana Basal Glomerular/patologia , Rim/patologia , Adolescente , Adulto , Doença Antimembrana Basal Glomerular/imunologia , Proteínas do Sistema Complemento/análise , Imunofluorescência , Humanos , Imunoglobulinas/análise , Rim/imunologia , Masculino
9.
Am J Med ; 75(6): 920-7, 1983 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6359877

RESUMO

A prospective trial of warfarin and dipyridamole was performed in patients with membranoproliferative glomerulonephritis. Eighteen completed either a control or treatment year, and 13 completed both a control and treatment year. To obviate the bias of excluding control patients who had renal failure after one year, both an unpaired and a paired analysis were performed. The unpaired analysis compared 10 patients followed for an initial control year with eight patients receiving treatment first. Renal function remained stable over the year in the treated group, but worsened in the control group. Slopes of regression lines for reciprocal serum creatinine values were significantly different between groups (p less than 0.025). Urine protein excretion also decreased in the treated group. Four of 10 control patients had a two-fold increase in serum creatinine levels, but no treatment patient did. In the paired crossover analysis, significant differences in renal function were detected between control and treatment years in six patients whose renal function significantly changed over one of the years. In every instance, there was better preservation of renal function in the treatment year. Urinary protein also decreased significantly over the treatment year compared with the control year. Bleeding was the most frequent complication. These data suggest that warfarin and dipyridamole have a beneficial effect on renal function in membranoproliferative glomerulonephritis.


Assuntos
Dipiridamol/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Varfarina/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Creatinina/sangue , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Estudos Prospectivos
10.
Biochem Pharmacol ; 31(4): 561-6, 1982 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-6279108

RESUMO

Rainbow trout (Salmo gairdneri) held at 7 degrees and 16 degrees were given Aroclor 1254 (PCB) (10 mg/kg body wt) via intraperitoneal injections. The binding of [3H]benzo[a]pyrene (BaP) to deproteinized salmon sperm DNA was assayed (pmoles BaP equivalents per mg DNA per mg protein) using the post-mitochondrial supernatant (S 10) fractions from livers of fish at 24-168 hr after the PCB exposure. Liver enzymes from the untreated fish acclimated at 7 degrees yielded an average binding value (0.37 +/- 0.17) which was significantly greater (P less than 0.05) than the value (0.07 +/- 0.03) for untreated fish at 16 degrees. Liver supernatant fractions from PCB-induced fish acclimated at 16 degrees and sampled at 24-120 hr showed a substantial increase (P less than 0.05) in the binding (average value 2.4 +/- 1.8) compared to the value obtained with untreated fish at 16 degrees. At 24, 48 and 120 hr after the PCB treatment of fish held at 7 degrees, there was no significant increase in the binding value or extent of metabolism of BaP compared to that obtained with the untreated fish at 7 degrees. However, at 168 hr, three of four fish at 7 degrees responded to the PCB treatment with significantly (P less than 0.05) increased binding values (3.3 +/- 1.6). Chromatographic analyses of the ethyl acetate-soluble metabolites revealed that 3-hydroxy BaP and 7,8- and 9,10-dihydrodiols were the major metabolites; K-region metabolites were formed in trace amounts in untreated and PCB-treated fish at both temperatures. No marked qualitative differences were observed in metabolite profiles after the PCB treatment; however, overall metabolism of BaP and production of reactive metabolites by liver enzymes were considerably (P less than 0.05) enhanced in the PCB-induced fish at both 7 degrees and 16 degrees.


Assuntos
Benzopirenos/metabolismo , Carcinógenos/metabolismo , Poluentes Ambientais/farmacologia , Fígado/metabolismo , Bifenilos Policlorados/farmacologia , Salmonidae/metabolismo , Temperatura , Truta/metabolismo , Animais , Benzo(a)pireno , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , DNA/metabolismo
11.
Biochem Pharmacol ; 34(2): 263-8, 1985 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-4038451

RESUMO

Tritiated benzo[a]pyrene (BaP) and (+/-)-7,8-dihydroBaP (BaP 7,8-dihydrodiol) were incubated with English sole liver microsomes in the presence of salmon testes DNA. The modified deoxynucleosides were isolated by Sephadex LH-20 column chromatography and analyzed by reverse-phase high-pressure liquid chromatography (HPLC). A single, major adduct (60-68% of the total modified deoxynucleosides) was formed when either BaP or BaP 7,8-dihydrodiol was incubated with sole liver microsomes and DNA. Although other minor BaP-DNA adducts were formed, none represented greater than 3% of the total adducts. The major adduct had a retention time on HPLC identical to that of the N2-[10 beta (7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxy-guanosine (7R-anti-BPDE/trans-dG) adduct formed when anti-BPDE, the ultimate carcinogen of BaP in mammals, was incubated with DNA. Analysis of the Bay region tetrols showed that only the 7 alpha, 8 beta, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP, a hydrolysis product of the anti-BPDE, was formed when BaP was incubated with sole liver microsomes. When BaP 7,8-dihydrodiol was used as the substrate, the 7 alpha, 8 beta, 9 beta, 10 alpha-, 7 alpha, 8 beta, 9 alpha, 10 beta-, and 7 alpha, 8 beta, 9 alpha, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP's were formed, indicating the formation of both anti- and syn-BPDE. The ratio of tetrols of anti-BPDE/syn-BPDE was 2; however, the ratio of adducts of anti-BPDE/syn-BPDE was 20. Thus, the findings show that hepatic microsomes of English sole, a fish species having a high incidence of liver neoplasia in chemically contaminated estuaries, metabolized BaP and BaP 7,8-dihydrodiol stereoselectively to form predominantly the 7R-anti-BPDE/trans-dG adduct.


Assuntos
Benzo(a)pireno/metabolismo , DNA/metabolismo , Di-Hidroxi-Di-Hidrobenzopirenos , Peixes/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Benzopirenos/metabolismo , Técnicas In Vitro
12.
Environ Health Perspect ; 90: 93-100, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2050086

RESUMO

Studies with several bottom fish species from urban waterways show that of the identified xenobiotic chemicals in bottom sediments, polycylic aromatic hydrocarbons (PAHs) are the most strongly associated with the prevalence of liver lesions, including neoplasms. Accordingly, there is concern about the transfer of contaminants, such as PAHs, from aquatic species to humans. Because PAHs exert their toxicity only after being biotransformed, increasing attention has been focused on the ability of aquatic organisms to metabolize these chemicals. Overall, the results of both laboratory and field studies show that generally low levels (nanograms per gram wet weight) of a few low molecular weight PAHs may be present in edible tissue of fish from contaminated areas and that high molecular weight PAHs, such as the carcinogen benzo(a)pyrene, will rarely be detected because of extensive metabolism. Additionally, the results from a few studies suggest that even though interactions between xenobiotics can affect both biochemical and physiological systems to alter the disposition of PAHs in fish, these interactions do not markedly change the relative proportions of metabolites to parent PAH in tissues. Thus, these studies clearly demonstrate that to obtain some insight into the questions of whether there is any risk to human health from consuming fish and crustaceans from urban areas, techniques must be developed that measure metabolites of carcinogens, such as PAHs, in edible tissue. Initial attempts may focus on semiquantitative methods that permit rapid assessment of the level of metabolites in edible tissues of fish and crustaceans from many urban areas.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Carcinógenos/farmacocinética , Peixes/metabolismo , Compostos Policíclicos/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Biotransformação , Carcinógenos/metabolismo , Contaminação de Alimentos/análise , Compostos Policíclicos/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Environ Health Perspect ; 102 Suppl 12: 19-23, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7713027

RESUMO

The recent development of techniques to measure levels of carcinogens covalently bound to DNA provides the opportunity to use DNA adducts as molecular dosimeters of exposure to environmental carcinogens and mutagens. This is especially important because epizootiologic studies have shown a positive association between environmental carcinogens, such as polycyclic aromatic hydrocarbons, and increased prevalence of neoplasms and related lesions, primarily in liver, of benthic fish species from a wide range of urban and industrialized areas. In studies with wild fish and mammalian species the 32P-postlabeling assay, as developed for aromatic compounds, has been used most extensively because of its high sensitivity and ability to detect structurally uncharacterized adducts. The results to date of field and laboratory studies show that hepatic DNA adducts detected in fish are associated with increased exposure to environmental polycyclic aromatic compounds in the preponderance of species examined, whereas in the limited studies with wild mammals, such a relationship is equivocal at present. The findings with fish suggest that DNA adducts, as measured by 32P-postlabeling, have the potential to be effective molecular dosimeters of exposure to environmental carcinogenic aromatic compounds and thereby may lead to an improved understanding of the etiology of neoplasia in wild teleosts.


Assuntos
Carcinógenos Ambientais/análise , Adutos de DNA/efeitos dos fármacos , Monitoramento Ambiental , Peixes/genética , Mutagênicos/análise , Animais , Arvicolinae/genética , Carcinógenos Ambientais/efeitos adversos , Dano ao DNA , Mutagênicos/efeitos adversos , Baleias/genética
14.
Environ Health Perspect ; 71: 155-70, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3297658

RESUMO

The high prevalence of liver neoplasms in English sole (Parophrys vetulus) and substantially lower prevalence of neoplasms in a closely related species, starry flounder (Platichthys stellatus) captured from industrialized waterways, provide a unique opportunity to compare biochemical processes involved in chemical carcinogenesis in feral fish species. Because levels of aromatic hydrocarbons (AHs) in urban sediments are correlated with prevalences of liver neoplasms in English sole, we have initiated detailed studies to evaluate the effects of endogenous and exogenous factors on uptake, activation and detoxication of carcinogenic AHs, such as benzo[a]pyrene (BaP), using spectroscopic, chromatographic, and radiometric techniques. The results obtained thus far show that sole readily takes up AHs associated with sediment from urban areas and that the presence of other xenobiotics, such as PCBs, in sediment increases tissue concentrations of BaP metabolites. Extensive metabolism of BaP occurred whether sole was exposed to this AH via sediment, per os, or intraperitoneally. Substantial modification of hepatic DNA occurred and persisted for a period of 2-4 weeks after a single exposure to BaP. The level of covalent binding of BaP intermediates to hepatic DNA was 10-fold higher in juvenile than adult sole and 90-fold higher in juvenile sole than in Sprague-Dawley rat, a species which is resistant to BaP-induced hepatocarcinogenesis. The level of chemical modification of hepatic DNA in juvenile flounder was 2-4 fold lower than that for juvenile sole and concentration of BaP 7,8-diol glucuronide in bile of sole was significantly higher than that in flounder bile, although the rate of formation of BaP 7,8-diol by hepatic microsomes was comparable for both species. Moreover, liver microsomes from both species, in the presence of exogenous DNA, metabolized BaP into essentially a single adduct, identified as (+)anti-7,8-diol-9,10-epoxy-7,8,9,10-tetrahydroBaP-dG. These results, along with our findings that hepatic GST activity in flounder was two times higher than in sole, demonstrate that microsomal metabolism of BaP does not accurately reflect the differences in the ability of these fish to form BaP-DNA adducts in vivo and also suggest that detoxication of reactive intermediates is an important factor in determining the levels of DNA modification by AHs and resulting toxic effects in feral fish.


Assuntos
Carcinógenos/toxicidade , Peixes/metabolismo , Animais , Biotransformação , Carcinógenos/metabolismo , Inativação Metabólica
15.
Environ Health Perspect ; 102(2): 200-15, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8033852

RESUMO

Relationships between hepatic lesions and chemical contaminant concentrations in sediments, stomach contents, liver tissue, and bile were statistically evaluated in three species of bottomfish, English sole (Pleuronectes vetulus), starry flounder (Platichthys stellatus), and white croaker (Genyonemus lineatus), captured from 27 urban and nonurban sites on the Pacific Coast from Alaska to southern California. Lesions detected were neoplasms, preneoplastic foci of cellular alteration, nonneoplastic proliferative lesions, unique or specific degenerative/necrotic lesions, nonspecific degenerative/necrotic lesions, and hydropic vacuolation of biliary epithelial cells and hepatocytes. In general, lesion prevalences were significantly higher in all three species captured at chemically contaminated urban sites, and certain lesions had significantly higher relative risks of occurrence at urban sites in Puget Sound, San Francisco Bay, the vicinity of Los Angeles, and San Diego Bay. Concentrations of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, DDT and its derivatives, and chlordanes and dieldrin in sediment, stomach contents, liver, and fluorescent aromatic compounds in bile were significant risk factors for the occurrence of neoplastic, preneoplastic, nonneoplastic proliferative, and specific degenerative/necrotic lesions, as well as hydropic vacuolation. Fish age also had a significant influence on occurrence of several hepatic lesions, but gender was rarely a significant risk factor. These relationships provide strong evidence for the involvement of environmental contaminants in the etiology of hepatic lesions in several marine bottomfish species and clearly indicate the utility of these lesions as biomarkers of contaminant-induced effects in wild fish.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Monitoramento Ambiental , Peixes/metabolismo , Linguado/metabolismo , Poluentes Químicos da Água/efeitos adversos , Animais , Bile/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Monitoramento Epidemiológico , Feminino , Mucosa Gástrica/metabolismo , Fígado/metabolismo , Modelos Logísticos , Masculino , Oceano Pacífico , Prevalência , Fatores de Risco , Poluentes Químicos da Água/farmacocinética
16.
J Am Geriatr Soc ; 27(9): 407-9, 1979 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-469153

RESUMO

An 86-year-old man with previous normal renal function was hospitalized because of renal insufficiency. He had a long history of atherosclerotic heart disease, mild hypertension and pulmonary embolism, requiring anticoagulant therapy. In view of the normal-sized kidneys and absence of casts in the urinary sediment, a diagnosis of atheroembolic renal disease was made. The patient's renal function deteriorated, but he refused hemodialysis. Death occurred within a few weeks. At autopsy, severe aortic atherosclerosis was observed and atheroembolic renal disease was confirmed as the cause of renal failure. Occasionally, renal failure can be the sole manifestation of spontaneous atheroembolic disease. This possibility should be considered if the physician is called upon to establish the diagnosis when renal insufficiency develops in atherosclerotic patients.


Assuntos
Injúria Renal Aguda/etiologia , Arteriosclerose/complicações , Embolia/complicações , Injúria Renal Aguda/patologia , Fatores Etários , Idoso , Doenças da Aorta/complicações , Arteriosclerose/patologia , Doença das Coronárias/complicações , Embolia/patologia , Humanos , Masculino
17.
Chem Phys Lipids ; 31(3): 237-44, 1982 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7172342

RESUMO

Physical properties (e.g. specific gravity, adiabatic compressibility and sound velocity) of lipids isolated from tissues from contiguous areas of the fatty melon of an echo-locating porpoise (Delphinus delphis) were determined to elucidate relations between lipid composition and structure, and sound transmission in the head. Lipid content varied greatly within the melon (13.6-77.6% of the tissue weight) and triacylglycerols (80-100%) were the major lipid components. This lipid class was composed of diisovaleroylglycerides (triacylglycerols containing two isovaleroyl moieties and a long-chain acyl moiety), monoisovaleroyldiacylglycerols and triacylglycerols consisting of long-chain acids. The lipid-rich (greater than 45%) areas in the melon contained a high proportion (greater than 45% of total triacylglycerols) of diisovaleroylglycerides. There were gradations of sound velocities within the melon; the lowest sound velocities were associated with high concentrations of diisovaleroylglycerides (less than 1400 m/s) and the highest with high concentrations of long-chain triacylglycerols. Assuming an average sound frequency of 75 kHz, and considering dimensions of melon (path length and width of 12-14 cm and 5 cm, respectively), a forward radiating lobe of 15-25 degrees is produced. Thus, the deposition of lipids of different acoustic properties in a three-dimensional matrix within the porpoise melon results in a lens for the projection of sound into the marine environment.


Assuntos
Golfinhos/fisiologia , Audição , Valeratos/fisiologia , Animais , Técnicas In Vitro , Som , Triglicerídeos/isolamento & purificação , Triglicerídeos/fisiologia
18.
Rev Environ Contam Toxicol ; 143: 79-165, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7501868

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the marine environment, occurring at their highest environmental concentrations around urban centers. While they can occur naturally, the highest concentrations are mainly from human activities, and the primary sources are combustion products and petroleum. Two factors, lipid and organic carbon, control to a large extent the partitioning behavior of PAHs in sediment, water, and tissue; the more hydrophobic a compound, the greater the partitioning to these phases. These two factors, along with the octanol-water partition coefficient, are the best predictors of this partitioning and can be used to determine PAH behavior and its bioavailability in the environment. It is well known that the lipid of organisms contains the highest levels of hydrophobic compounds such as PAHs, and that organic carbon associated with sediment or dissolved in water can have the greatest influence on PAH bioavailability. Partitioning of combustion-derived PAHs between water and sediment may be much less than predicted, possibly because associations with particles are much stronger than expected. This reduced partitioning may produce erroneous results in predicting bioaccumulation where uptake from water is important. Accumulation of PAHs occurs in all marine organisms; however, there is a wide range in tissue concentrations from variable environmental concentrations, level and time of exposure, and species ability to metabolize these compounds. PAHs generally partition into lipid-rich tissues, and their metabolites can be found in most tissues. In fish, liver and bile accumulate the highest levels of parent PAH and metabolites; hence, these are the best tissues to analyze when determining PAH exposure. In invertebrates, the highest concentrations can be found in the internal organs, such as the hepatopancreas, and tissue concentrations appear to follow seasonal cycles, which may be related to variations in lipid content or spawning cycles. The major route of uptake for PAHs has been debated for years. For the more water-soluble PAHs, it is believed that the main route of uptake is through ventilated water and that the more hydrophobic compounds are taken in mainly through ingestion of food or sediment. There are many variables, such as chemical hydrophobicity, uptake efficiency, feeding rate, and ventilatory volume, which may affect the outcome. The route of uptake may be an important issue for short-term events; however, under long-term exposure and equilibrium conditions between water, prey, and sediment, the route of uptake may be immaterial because the same tissue burdens will be achieved regardless of uptake routes.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Disponibilidade Biológica , Peixes , Invertebrados , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade
19.
Chem Biol Interact ; 80(3): 317-26, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1954659

RESUMO

Juvenile English sole were exposed intramuscularly to nitrofurantoin (NF) and the levels of 8-hydroxy-2' deoxyguanosine (8-OH-dG) in liver, kidney and blood were determined using reversed-phase HPLC with electrochemical detection. Identification and quantitation of the 8-OH-dG in the samples was accomplished by comparison with standard 8-OH-dG, which was characterized by UV spectroscopy and fast-atom bombardment mass spectrometry. The levels of hepatic 8-OH-dG increased (r2 = 0.59, P = 0.015) with the dose of NF (0.10-10 mg NF/kg fish). In kidney and blood, however, the levels of 8-OH-dG were significantly higher than controls only at the highest dose tested. The level of binding in liver ranged from 0.37 to 0.76 fmol 8-OH-dG/micrograms DNA. The levels of hepatic 8-OH-dG reached a maximum (approx. 1 fmol 8-OH-dG/micrograms DNA) between 1 and 3 days after exposure, followed by a decrease to control levels (approx. 0.25 fmol 8-OH-dG/micrograms DNA) at 5 days post-exposure. These data demonstrate the first direct evidence for the formation of oxidized DNA bases resulting from the metabolism of a nitroaromatic compound by fish.


Assuntos
Dano ao DNA , Desoxiguanosina/análogos & derivados , Nitrofurantoína/toxicidade , 8-Hidroxi-2'-Desoxiguanosina , Animais , Cromatografia Líquida de Alta Pressão , DNA/metabolismo , Desoxiguanosina/sangue , Desoxiguanosina/síntese química , Desoxiguanosina/metabolismo , Linguados/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Espectrometria de Massas , Oxirredução , Espectrofotometria Ultravioleta
20.
Chem Biol Interact ; 88(1): 55-69, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8330324

RESUMO

The formation and persistence of benzo[a]pyrene (BaP)- and 7H-dibenzo[c,g]-carbazole (DBC)-DNA adducts in liver of English sole (Pleuronectes vetulus) were investigated. BaP is a putative hepatocarcinogen in English sole based on its ability to induce formation of preneoplastic foci, while DBC is a hepatocarcinogen in mammals but whose carcinogenicity in fish is not known. English sole liver was sampled from 2 h through 84 days after a single intermuscular injection of a BaP and DBC mixture (100 mumol of each/kg body wt.), and DNA adduct levels were measured by the nuclease P1 version of the 32P-postlabeling assay. The major BaP adducts detected were from binding of BaP-7,8-diol-9,10-epoxide to DNA, whereas multiple uncharacterized DBC-DNA adducts were detected. Total adduct levels for both BaP and DBC reached a maximum at 2 days post exposure. The levels of DBC-DNA adducts were greater than the levels of BaP adducts at all time points and increased more rapidly than did the levels of BaP-DNA adducts. The DBC to BaP adduct ratio was 33 +/- 8.8 at 2 h and declined to 4.2 +/- 0.48 by 12 h post exposure. From 2 to 28 days, the levels of both BaP and DBC adducts declined with apparent half-lives of 11 and 13 days, respectively. There was no apparent decline from 28 to 84 days in the levels of the remaining BaP or DBC adducts; these persistent adducts represented 32 and 36% of maximum levels, respectively. These results provide the first data on the kinetics of adduct formation and removal of a carcinogenic nitrogen-containing polycyclic aromatic compound in fish. The results showing greater binding and similar persistence of DBC-DNA adducts compared to BaP-DNA adducts suggest that DBC may be hepatotoxic and potentially carcinogenic in English sole. In a separate experiment, the effect of multiple doses of BaP (30 mumol/kg body wt.) on the levels of hepatic BaP-DNA adducts showed that adduct levels increased linearly (r = 0.815, P = 0.0007) with 5 successive doses administered at 2 day-intervals and sampled 2 days after the last dose. The persistence of both BaP-DNA and DBC-DNA adducts in liver, together with the increase in BaP-DNA adducts in English sole exposed to successive doses of BaP, suggest that hepatic xenobiotic-DNA adducts in English sole are molecular dosimeters of relatively longterm environmental exposure to genotoxic polycyclic aromatic compounds.


Assuntos
Benzo(a)pireno/toxicidade , Carbazóis/toxicidade , Carcinógenos/toxicidade , DNA/efeitos dos fármacos , Animais , DNA/análise , Sinergismo Farmacológico , Peixes , Marcação por Isótopo , Fígado/efeitos dos fármacos , Radioisótopos de Fósforo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA