Реферат
OBJETIVO: Avaliar as repercussões hepáticas da carcinogênese colônica induzida por diferentes doses e tempos de exposição ao azoximetano em ratos Wistar. MÉTODOS: Quarenta e quatro ratos foram distribuídos em quatro grupos. Os animais tinham oito semanas no início do experimento. No grupo 1, receberam 1.0mL de solução salina intraperitonealmente uma vez por semana por duas semanas. No grupo 2, receberam 15 mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 15ª semana do experimento. Os animais do grupo 3 receberam solução salina intraperitonealmente uma vez por semana por duas semanas. Os animais do grupo 4 receberam 20mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 26ª semana do experimento. Os fragmentos de tecido hepático foram corados pela hematoxilina e eosina e avaliadas microscopicamente. RESULTADOS: Grupo 1 e grupo 2 diferiram significantemente em relação a esteatose, mas não houve diferença entre o grupo 3 e o grupo 4. No entanto, no grupo 4 foram observadas lesões pré-neoplásicas (focos de células alteradas, claras, vacuoladas, basofílicas, anfofílicas, tigróides, oncocíticas, pequenas ou acidófilas, espongioses e pelioses) e lesões neoplásicas (colangiomas e adenomas) contendo hepatócitos atípicos de permeio, não identificados no grupo 3. CONCLUSÃO: No modelo de carcinogênese colorretal, lesões hepáticas pré-neoplásicas e neoplásicas aparecem e evoluem na proporção do tempo e dose de exposição ao azoximetano.
OBJECTIVE: To evaluate the hepatic effects of colonic carcinogenesis induced by azoxymethane at different doses and times of exposure in rats. METHODS: Forty-four Wistar rats were divided into four groups. The animals were eight weeks at the beginning of the experiment. group 1 received 1.0ml of saline intraperitoneally once a week for two weeks. Group 2 received 15 mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 15th week of the experiment. The animals of group 3 received saline intraperitoneally once a week for two weeks. Group 4 animals received 20mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 26th week of the experiment. The fragments of liver tissue were stained with hematoxylin and eosin and evaluated microscopically. RESULTS: Groups 1 and 2 differed significantly in relation to steatosis, no difference having been found between group 3 and group 4. However, in group 4 we observed pre-neoplastic lesions (foci of altered, clear, vacuolated, basophilic, amphophilic tigroid, oncocytic, small or acidophilus cells, spongiosis and peliosis) and neoplastic lesions (adenomas and colangiomas) containing atypical hepatocytes in between, not identified in group 3. CONCLUSION: In the model of colorectal carcinogenesis, preneoplastic and neoplastic hepatic lesions appear and evolve in proportion to the time of exposure and dose of azoxymethane.
Тема - темы
Animals , Rats , Azoxymethane/administration & dosage , Carcinogenesis/drug effects , Carcinogens/administration & dosage , Colorectal Neoplasms/chemically induced , Colorectal Neoplasms/complications , Liver Diseases/etiology , Precancerous Conditions/etiology , Azoxymethane/pharmacology , Carcinogens/pharmacology , Liver Diseases/pathology , Rats, WistarРеферат
It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg-1 day-1 ß-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70 percent in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78 percent increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.
Тема - темы
Animals , Male , Rats , Antioxidants/analysis , Carotenoids/blood , DNA Damage/drug effects , Oxidative Stress/drug effects , Prostate/drug effects , beta Carotene/blood , Chromatography, High Pressure Liquid , Carcinogens/pharmacology , Carotenoids/analysis , DNA , Deoxyguanosine/analysis , Deoxyguanosine/analogs & derivatives , Ferric Compounds/pharmacology , Nitrilotriacetic Acid/analogs & derivatives , Nitrilotriacetic Acid/pharmacology , Prostate/chemistry , Prostate/pathology , Rats, Wistar , beta Carotene/analysisРеферат
An environmental pollutant, tetrachloro dibenzo dioxin (TCDD) is known to illicit the cognitive disability and motor dysfunction in the developing brain. TCDD induced effects leading to neurodevelopmental and neurobehavioral deficit may have been defined, however underlying molecular mechanism and possible intracellular targets remain to be elucidated. In this study, we attempted to analyze TCDD-induced neurotoxic effects in the granule cells from cerebellum where certain cognitive abilities and motor function command are known to be excuted. [3H]PDBu, (phorbol 12,13-dibutyrate) binding assay indicated that TCDD induced a dose-dependent increase of total PKC activity and its induction was the aryl hydrocarbon receptor (AhR) dependent and N-methyl-D-aspartate receptor (NMDAR) independent. TCDD also caused the translocation of both PKC-alpha and -epsilon in a dose-dependent manner but associated with different receptors; PKC-alpha via AhR but not PKC-epsilon indicating an isozyme-specific pattern of the induction. Increase of the ROS formation was also observed in the cells treated with TCDD in a dose-dependent and an AhR-dependent manner. The treatment of the cells with the diamino dicyano-bis(2-aminophenylthio) butadiene (U0126, MEK-1/2 inhibitor), dizocilpine maleate (MK-801, non-competitive N-methyl-D-aspartate glutamate receptor antagonist) and vitamin E attenuated the TCDD-induced ROS production indicating that TCDD-induced ROS formation may be associated with activation of ERK-1/2 in the MAP kinase pathway or the NMDA receptor. TCDD also increased [Ca2+]i, which is associated with ROS formation and PKC activation in the cerebellar granule cells. It is suggested that TCDD activates the NMDA receptor, which may induce a sustained increase of [Ca2+]i in neurons followed by the ROS formation. Our findings may contribute to understanding the mechanism of TCDD-related neurotoxicity, thereby improving the health risk assessment of neurotoxic compounds in humans.
Тема - темы
Animals , Rats , Binding, Competitive , Butadienes/pharmacology , Carcinogens/pharmacology , Cerebellum/cytology , Dizocilpine Maleate/pharmacology , Environmental Pollutants/toxicity , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Neuroprotective Agents/pharmacology , Nitriles/pharmacology , Phorbol 12,13-Dibutyrate/pharmacology , Protein Kinase C/metabolism , Protein Transport , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Polychlorinated Dibenzodioxins/toxicityРеферат
Evidences show that eukaryotic mRNAs can perform protein translation through internal ribosome entry sites (IRES). 5'-Untranslated region of the mRNA encoding apoptotic protease-activating factor 1 (Apaf-1) contains IRES, and, thus, can be translated in a cap-independent manner. Effects of changes in protein translation pattern through rapamycin pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-butanone(NNK, tobacco-specific lung carcinogen)-induced apoptosis in human bronchial epithelial cells were examined by caspase assay, FACS analysis, Western blotting, and transient transfection. Results showed that NNK induced apoptosis in concentration- and time-dependent manners. NNK-induced apoptosis occurred initially through cap-independent protein translation, which during later stage was replaced by cap-dependent protein translation. Our data may be pplicable as the mechanical basis of lung cancer treatment.
Тема - темы
Humans , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptotic Protease-Activating Factor 1 , BH3 Interacting Domain Death Agonist Protein , Blotting, Western , Bronchi/metabolism , Carcinogens/pharmacology , Carrier Proteins/metabolism , Caspases/metabolism , Cytochromes c/metabolism , Dose-Response Relationship, Drug , Epithelial Cells/metabolism , Eukaryotic Initiation Factor-4E/metabolism , Flow Cytometry , Nitrosamines/pharmacology , Protein Biosynthesis , Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Cap-Binding Proteins/physiology , Sirolimus/pharmacology , Time Factors , bcl-2-Associated X ProteinРеферат
In order to determine the organ specific carcinogenicity of benzo(a)pyrene (B(a)P), its metabolites, formed in vitro by incubation with the homogenates from liver, lungs, kidneys, intestine and brain of rats, were isolated by TLC and spectroscopy. B(a)P was found to be converted into a number of metabolites by different tissue homogenates. The results showed that the proximate carcinogenic metabolite, 7,8-dihydro-7,8-dihydroxy B(a)P was formed only when rat lung and kidney homogenates were incubated with B(a)P in vitro. The UV spectral analysis also confirmed the formation of this metabolite only on incubation of B(a)P with rat lung and kidney homogenates. As the proximate carcinogenic metabolite was only formed by incubating B(a)P with the homogenates from target organs, its organ specific carcinogenicity may be explained.
Тема - темы
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism , Animals , Benzo(a)pyrene/pharmacology , Brain/drug effects , Carcinogens/pharmacology , Chromatography, Thin Layer , Intestines/drug effects , Kidney/drug effects , Liver/drug effects , Lung/drug effects , Organ Specificity/drug effects , Rats , Rats, Wistar , Spectrophotometry, UltravioletРеферат
A close correlation between vitamin D receptor (VDR) abundance and cell proliferation rate has been shown in NIH-3T3 fibroblasts, MCF-7 breast cancer and in HL-60 myeloblastic cells. We have now determined if this association occurs in other leukemic cell lines, U937 and K562, and if VDR content is related to c-myc expression, which is also linked to cell growth state. Upon phorbol myristate acetate (PMA) treatment, cells from the three lineages (HL-60, U937 and K562) differentiated and expressed specific surface antigens. All cell lines analyzed were growth inhibited by PMA and the doubling time was increased, mainly due to an increased fraction of cells in the G0/G1 phase, as determined by flow cytometry measurements of incorporated bromodeoxyuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in leukemic cell lines, as determined by immunofluorescence and Northern blot assays, was not consistently changed upon inhibition of cell proliferation since VDR levels were down-regulated only in HL-60 cells. Our data suggest that VDR expression cannot be explained simply as a reflection of the leukemic cell growth state.
Тема - темы
Humans , Carcinogens/pharmacology , Cell Differentiation/physiology , Gene Expression Regulation, Neoplastic/physiology , Leukemia/genetics , Receptors, Calcitriol/genetics , Tetradecanoylphorbol Acetate/pharmacology , Antibodies, Monoclonal , Cells, Cultured , Down-Regulation , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic/drug effects , Growth Inhibitors , HL-60 Cells , K562 Cells , Phenotype , Receptors, Calcitriol/drug effects , RNA/isolation & purification , U937 CellsРеферат
Estudou-se de forma comparativa, os efeitos de peróxido de hidrogênio sobre a mucosa bucal de hamsters. Utilizou-se 96 animais, divididos em 8 grupos, aplicando-se: água destilada; DMBA; peróxido de carbamida a 10 por cento com carbopol; peróxido de hidrogênio a 27 por cento; dentifrício com peróxido de hidrogênio; DMBA+peróxido de carbamida a 10 por cento com carbopol; DMBA+peróxido de hidrogênio a vinte e sete por cento; DMBA+dentifrício com peróxido de hidrogênio. Pode-se constatar que o peróxido de hidrogênio, nas várias formas aplicadas, näo induziu alteraçöes epiteliais de nenhuma natureza e morfologicamente detectáveis à microscopia óptica de luz. Os mesmos produtos, aplicados após o DMBA, aumentaram o número de animais mais severamente comprometidos e promoveram lesöes carcinomatosas mais amplas e severas na mucosa, quer seja do ponto de vista macro ou microscópico. Concluiu-se que o peróxido de hidrogênio atua como agente promotor da carcinogênese, pois potencializa o efeito de agentes iniciadores na carcinogênese bucal química
Тема - темы
Animals , Male , Female , Infant , Cricetinae , Mouth Mucosa/drug effects , Hydrogen Peroxide/pharmacology , 9,10-Dimethyl-1,2-benzanthracene/pharmacology , Carcinogens/classification , Carcinogens/pharmacology , Dentifrices/pharmacology , Distilled Water , Pathology, Oral , Peroxides/classification , Peroxides/pharmacologyРеферат
To evaluate the induction of preneoplastic hepatic foci in relation to natural killer cell (NK) activity, we sequentially analyzed glutathione S-transferase placental form positive (GST-P+) hepatocytes and NK activity during diethylnitrosamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis in Sprague-Dawley rats. Previous studies have shown that NK activity can modulate the carcinogenic process induced by chemical carcinogens. Newborn females were initially given a single intraperitoneal injection of 15 mg DEN/kg and three weeks later, they were treated with 500 ppm phenobarbital (PB). From week 3, PB was administered in drinking water for 9 weeks. Interim and terminal sacrifices were performed at weeks 12, 15 and 30. GST-P+ hepatocytes increased with age in DEN-treated rats, especially in the population of more than two GST-P+ hepatocytes. The NK activity of DEN-treated rats did not significantly differ from that of control rats until week 12, but it progressively decreased from week 15 to 30. These results indicate that changes of NK activity inversely correlated with the induction of preneoplastic hepatic foci. This strong correlation of decreased NK activity with enhanced induction of GST-P+ foci suggests that NK activity is important in the early progression of hepatocarcinogenesis in rats.
Тема - темы
Female , Rats , Animals , Body Weight , Carcinogens/pharmacology , Diethylnitrosamine/pharmacology , Glutathione Transferase/metabolism , Killer Cells, Natural/immunology , Liver/enzymology , Liver/cytology , Liver Neoplasms/physiopathology , Organ Size , Placenta , Rats, Sprague-DawleyРеферат
The effect of the administration of seven doses of the hepatocarcinogen thioacetamide on the chemical composition of rat liver nuclear envelope subfractions: associated chromatin, nuclear membranes and pore complex-lamina fraction, is analyzed. No alteration in DNA, RNA or phospholipid content is observed after the hepatocarcinogen treatment. Electrophoretic studies of each subfraction from thioacetamide treated rats show differences in the relative proportions of some polypeptides when compared with the controls. Examination of the wheat germ agglutinin binding polypeptides of each subfraction reveals a decrease in the stain of two pore complex-lamina nucleoporins of 85 and 164 kDa and an increase in one of 93 kDa; this observation can be due to changes in the quantity and/or in the agglutinin binding capacity of the nucleoporin as a result of thioacetamide administration. In view of the participation of nucleoporins in the nucleocytoplasmic transport, the changes observed suggest a relationship between changes of some O-linked N-acetyl glucosamine polypeptides components of the nuclear pore complex and the altered transport of some RNA species observed after thioacetamide administration.
Тема - темы
Animals , Male , Rats , Carcinogens/pharmacology , Liver/cytology , Nuclear Proteins/drug effects , Peptides/drug effects , Thioacetamide/pharmacology , Nuclear Envelope/chemistry , Nuclear Envelope/metabolism , Nuclear Proteins/chemistry , Peptides/chemistry , Rats, Sprague-DawleyРеферат
El principal objetivo del presente trabajo consistió en determinar los cambios histológicos en el epitelio del colon en primates de la especie Cebus apella inducidos mediante la administración de la 1,2-dimetilhidrazina (DMH). Fueron utilizados 12 primates, machos de 30 meses de edad y con un peso promedio de 2,800Kg. La DMH fue administrada por vía subcutánea a razón de 25 mg/Kg de peso corporal semanalmente, durante 16 semanas. Durante los 20 meses que duró la experiencia el peso corporal fue evaluado semanalmente en los primeros 4 meses y cada 30 días hasta el final del experimento. Al final de la experiencia, en cortes histológicos de 5 mum, coloreados con Hematoxilina-Eosina, fueron evaluados los cambios histológicos del epitelio intestinal, así como las mucosustancias, utilizándose las técnicas del PAS y Alcian blue e pH 2,5. El estudio histológico e histoquímico permitió caracterizar la morfología normal, así como las características de las mucosustancias en tres regiones: ciego, colon transverso y colon distal. Los cambios histológicos observados en los animales tratados con DMH consistieron en fenómenos de hiperplasia, displasia y disminución de las mucosustancias. Los cambios hiperplásicos comprometieron a las criptas glandulares y al epitelio superficial que reviste a los nódulos linfoides. Focos de displasia fueron observados en el colon transverso y última porción del colon distal y comprometieron a criptas localizadas tanto en profundidad como en criptas de la mucosa superficial. Se observaron criptas con disminución de mucosustancias neutras y ácidas. Nuestros resultados sugieren que la DMH indujo en el colon, focos displásicos y lesiones hiperplásicas en criptas y en el epitelio que reviste a los nódulos linfoides, así como disminución de las mucosustancias neutras y ácidas.
Тема - темы
Animals , Male , 1,2-Dimethylhydrazine/pharmacology , Carcinogens/pharmacology , Colon/drug effects , Colon/pathology , Cebus , Epithelium/drug effects , Epithelium/pathology , Hyperplasia/chemically induced , Hyperplasia/pathologyРеферат
Isolated rat liver mitochondria were incubated with various concentrations of aflatoxin B (AFB) for different periods of time. Respiration rates were then measured with two substrates (succinate and glutamate). State 3 respiration rate (with added ADP) declined with increase in preincubation concentrations of AFB1 (0.15-0.50 mM). On the other hand, state 4 respiration rate (after depletion of added ADP) was found to increase with increased pretreatment concentration of AFB. As a consequence, respiratory control index was reduced attaining minimum value with 0.25 mM AFB and preincubation time of 10 min. The induced anomaly in mitochondrial respiratory functions appear to be due to membrane damage caused by interaction of reactive AFB1 metabolite generated by mitochondrial cytochrome P-450 enzymes with mitochondrial components.
Тема - темы
Aflatoxin B1/pharmacology , Animals , Carcinogens/pharmacology , Cells, Cultured , Male , Mitochondria, Liver/drug effects , Oxygen Consumption/drug effects , Rats , Rats, WistarРеферат
Aflatoxin B1 (AFB1), a fungal toxin produced by Aspergillus flavus, is known to be a possible hepatocarcinogen. But the molecular biologic changes which may occur following exposure to AFB1 are not known and thus the carcinogenesis is not yet understood. This study was performed to examine the expressions of c-myc, c-fos and TGF-alpha genes and to investigate the possible role of those molecular biologic changes in hepatic regeneration and in the development of hepatocellular carcinoma (HCC). Sprague-Dawley rats were divided into 3 groups: Carbon tetrachloride (CCl4) only was administered to group I, AFB1 only was administered to group II and a combination of AFB1 and CCl4 was administered to group III. The animals were sacrificed at 0.5, 1, 2, 6, 12, 24, 48, and 72 hours after treatment. In addition to the examination of the hematoxylin-eosin stained sections, hepatic regeneration and apoptosis were analyzed quantitatively by bromodeoxyuridine (BrdU)-anti-BrdU immunohistochemistry and TUNEL assay utilizing apoptosis kit, respectively. The hepatic expressions of c-myc, c-fos and transforming growth factor-alpha (TGF-alpha) were examined by immunohistochemistry and studied by Western blot. The number of BrdU labelled cells and the degree of necrosis/apoptosis were comparable among the different groups. Livers of the group II rats showed nearly normal histology without regeneration and necrosis/apoptosis. In groups I and III, the number of BrdU- labelled cells showed an increase at 48 hours after treatment, and the increment was significantly higher in group I than in group III. Most BrdU-labelled cells were mature hepatocytes in group I, whereas in group III they appeared to be less mature. In group I, apoptosis showed an increase at around 24 hours, but appeared in group III as early as 12 hours after treatment and persisted through 48 hours. The expression of c-myc and c-fos were also different between the experimental groups. The expression intensity of c-myc in group I was highest at 1 hour and decreased thereafter. In groups II and III, the expressions were much more intense than in group I, except at 1 hour, and the increased intensity persisted throughout the experiment. Group II in particular showed a peak intensity at 30 minutes and at 6 hours after treatment. In group I, c-fos was strongly expressed only at 24 hours, but in group III, there was progressively increased expression with peak intensity at 24 hours. TGF-alpha was expressed in similar intensities in all groups throughout the experiment. These results suggest that AFB1 may evoke an intense and protracted expression of c-myc, provocating the CCl4-induced necrosis of hepatocytes, and a prolonged expression of c-fos, including persistent signals for regeneration which in turn may activate the replication of immature cells. These findings will aid further investigation of molecular biologic and histologic characteristics of the hepatotoxic and hepatocarcinogenic mechanism of AFB1 in rats. And these results in rats, together with clinico-epidemiologic and molecular biologic investigations in humans and other animals, suggest that AFB1 may supply hepatocarcinogenic background in early exposure time in AFB1-contaminated areas of China and Korea.
Тема - темы
Male , Rats , Aflatoxin B1/pharmacology , Animals , Carbon Tetrachloride , Carcinogens/pharmacology , Gene Expression/drug effects , Genes, Immediate-Early/drug effects , Liver Diseases/metabolism , Liver Diseases/genetics , Liver Diseases/chemically induced , Rats, Sprague-Dawley , Transforming Growth Factor alpha/metabolismРеферат
The mechanism by which an oxidant tumor promoter benzoyl peroxide (BP) influences signal transduction, was studied in promotion insensitive (P-), promotion sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. The basal levels of antioxidant enzymes CuZn-superoxide dismutase and catalase were higher in P+ and Tx JB6 cells. BP decreased the activities of these enzymes transiently in P+ and Tx cells, but induced them in P- JB6 cells. BP increased poly ADPR polymerase activity accompanied by a drop in NAD+ levels more significantly in P- JB6 cells, but did not affect PKC activity. It induced c-jun and c-fos gene expression in JB6 variants but to different extents, suggesting that it mediates its effects via genetic- epigenetic mechanism(s).
Тема - темы
Animals , Benzoyl Peroxide/pharmacology , Carcinogens/pharmacology , Cell Line , Epidermis/drug effects , Gene Expression Regulation/drug effects , MiceРеферат
There are several hydrazine derivatives with pharmacological activity, all of which have carcinogenic properties in experimental animals. Several mono- and disubstituted derivatives have been shown to produce carbon-centered radicals upon oxidation by enzymatic systems such as HbO2' Cytochrome P-450, monoamine oxidases, horseradish peroxidase and myeloperoxidase. Proposed mechanisms of hydrazine metabolism leading to alkylating species are discussed. The in vitro induction of DNA alterations by carbon-centered radicals generated in hydrazine metabolism ascertains the possibility of its occurrence in vivo. Our results, discussed herein, established the induction of cytotoxicity, proliferation and transformation of cultured mouse fibroblasts by systems in which hydrazine-derived alkyl radicals are formed. These studies represent another step towards distinguishing the possible involvement of metabolism-generated carbon-centered radicals in the onset of carcinogenic processes, which reinforces the importance of additional experimental approaches in order to consolidate this hypothesis.
Тема - темы
Carbon/chemistry , Carcinogens/pharmacology , Hydrazines/pharmacology , Carcinogens/metabolism , Carcinogens/toxicity , Cell Division , DNA Damage/drug effects , Fibroblasts/cytology , Fibroblasts/metabolism , Free Radicals , Hydrazines/metabolism , Hydrazines/toxicityРеферат
El presente trabajo fue realizado con el objetivo de estudiar el efecto por el lapachol (LAP) al ser administrado a rats en forma simultánea con un carcinógeno químico, el 20-merilcolantreno (MCA). Los animales fueron divididos en 4 lotes: A-Lote tratado con 80 mg de MCA (n=11 animales), B-Lote tratado con 80 mg de MCA+LAP 100 mg/Kg peso/día (n=15 animales), C-Lote tratado con LAP 100 mg/Kg peso día (n=12 animales), D-Lote control sin tratamiento (n=13 anisales). Los estudios citológicos así como la aplicación de técnicas citoquímicas permitieron conocer el diagnóstico de benegnidad o malignidad apenas producida la aparición del tumor. Estudios histopatológicos posteriores confiraaron la aparición el el 53 por ciento de los animales del lote B de tumores compatibles con adenocarcinomas pobremente diferenciados de glándula salival y en el 18.2 por ciento (2/11) de los animales del lote A de fibroadenomas de la glándula mamaria. Asimismo fue observada la presencia de uno o varios nódulos suprahepáticos en vencidad al ligamento suspensorio e histológicamente definidos como de hiperplasia nodular en el 33 por ciento (4/12) de los animales del lote C y en 13.3 por ciento (2/15) del B no produciéndose desarrollo de dichos nódulos en los lotes A y D. En el riñón fue observada dilatación quística de los túbulos en el 60 por ciento (9/15) y 83.3 por ciento (10/12) de los animales del lote B y C respectivamente. A partir del tumor primitivo de glándula salival fue desarrollada uma linea de tumores transplantables cuyo seguimiento fue realizado citológicamente. Se reafirma la importancia del diagnostico citológico e histopatológico para el estudio del efecto farmacológico de drogas que como el Lapachol son empleadas como antitumorales sin conocerse sus efectos nocivos.
Тема - темы
Rats , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Kidney Neoplasms/ultrastructure , Liver Neoplasms/ultrastructure , Lung Neoplasms/ultrastructure , Naphthoquinones/pharmacology , Neoplasms/chemically induced , Salivary Gland Neoplasms/ultrastructure , Carcinogens/pharmacology , Follow-Up Studies , Kidney Neoplasms/chemically induced , Liver Neoplasms/chemically induced , Lung Neoplasms/chemically induced , Methylcholanthrene/pharmacology , Rats, Sprague-Dawley , Salivary Gland Neoplasms/chemically inducedРеферат
In order to understand the possible mechanism(s) by which metanil yellow (MY) promotes liver tumour development, we have studied the effect of MY on DNA synthesis in primary cultures of normal rat hepatocytes, maintained under fully-defined conditions. MY alone was moderate, however, in combination with epidermal growth factor (EGF) showed synergism in markedly stimulating DNA synthesis which was dose-dependent. MY also showed stimulation of DNA synthesis either when added 16 h after the hepatocytes were primed with EGF or when first primed with MY for 16 h and then EGF was added. These observations suggest that the target site for MY action may be at the level of EGF-receptor of EGF-mediated early events. Further, MY induced DNA stimulation was found to be independent of insulin and dexamethasone. These results indicate that an important component of the tumour enhancement by MY may be its ability to cause an exaggerated version of the stimulation of DNA synthesis.
Тема - темы
Animals , Azo Compounds/pharmacology , Carcinogens/pharmacology , Cells, Cultured , DNA/biosynthesis , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , Epidermal Growth Factor/pharmacology , Insulin/pharmacology , Liver/drug effects , Male , Rats , Rats, Wistar , Stimulation, ChemicalРеферат
Five weeks treatment of male mice with 1,2-dimethylhydrazine leads to elevation in the level of diacylglycerol in liver. Increase in diacylglycerol content is accompanied by an increase in particulate activity of protein kinase C with a fall in its activity in cytosolic fraction. Quantitative analysis of neutral lipids of different subcellular fractions from liver reveals that diacylglycerol levels increases highly significantly in liver microsomal membranes of carcinogen treated mice. Separation of neutral lipids by thin layer chromatography indicates that also there is an increase in cholesterol esters in nuclei, mitochondria and microsomes of mice liver whereas monoacylglycerol almost disappeared in mitochondria and microsomes after DMH administration in comparison to their respective controls.
Тема - темы
1,2-Dimethylhydrazine , Animals , Carcinogens/pharmacology , Cholesterol Esters/metabolism , Diglycerides/metabolism , Dimethylhydrazines/pharmacology , Enzyme Activation , Liver/drug effects , Male , Mice , Protein Kinase C/metabolismРеферат
Atualmente, o método mais importante para a identificaçao de agentes químicos cancerígenos é o teste de longa duraçao in vivo, com roedores. No Brasil nao há condiçoes para a sua execuçao, devido à inexistência de especialistas e de infra-estrutura adequada. Em conseqüência, o país é dependente dos conhecimentos gerados no exterior sobre o risco que determinados compostos químicos impoem às populaçoes e ao meio ambiente. Por outro lado, as desvantagens inerentes ao protocolo deste teste, como a complexidade na execuçao, o tempo prolongado para obtençao das conclusoes e custo elevado, entre outras, levam à procura de alternativas mais convenientes. No presente trabalho sao apresentados dois testes in vivo para detecçao de cancerígenos químicos em ratos, que têm como vantagens o tempo de execuçao e o custo, menores que os do teste convencional. Os sistemas propostos têm só-o-fígado ou vários-órgaos-simultâneos como órgaos-alvo do eventual cancerígeno. Ambos os testes foram avaliados respectivamente com centenas e dezenas de substâncias químicas e reproduziram os resultados já obtidos em testes de longa duraçao, mostrando forte consistência biológica. Os autores destacam as vantagens de sua adoçao em países como o Brasil e propoem sua inclusao na seqüência de testes necessários para caracterizar um agente químico como cancerígeno.
Тема - темы
Animals , Rats , Carcinogens , Carcinogenicity Tests , Carcinogens/classification , Carcinogens/pharmacologyРеферат
Using incision, excision and dead space wound models in rats, a study was conducted on the effect of histamine on wound healing. Exogenous histamine given either ip or locally was without any effect. Semicarbazide as (histamine synthesis inhibitor) suppressed healing process (breaking strength of skin incision wound), decreased breaking strength and hydroxyproline content of granulation tissue and delay in period of epithelization. On the other hand compound 48/80 (a promoter of histamine forming capacity) was found to promote wound healing. Exogenous histamine (topical) reversed the anti-healing effect of semicarbazide on incision and excision wounds.
Тема - темы
Animals , Carcinogens/pharmacology , Female , Granulation Tissue/drug effects , Histamine/pharmacology , Male , Rats , Rats, Inbred Strains , Semicarbazides/pharmacology , Wound Healing/drug effects , p-Methoxy-N-methylphenethylamine/pharmacologyРеферат
Water, acetone and chloroform extracts of E. officinalis fruit reduced sodium azide and NPD induced his+ revertants significantly in TA100 and TA97 a strains respectively of S. typhimurium. The chloroform extract was less active as compared to water and acetone extracts. Autoclaving of water extract for 15 min did not reduce its activity. The enhanced inhibitory activity of the extracts on pre-incubation suggests the possibility of desmutagens in the extracts. Besides ascorbic acid, a constituent of the extract, the role of other antimutagenic factors in the extract cannot be ruled out.