RESUMO
One of the most important parasitic endemic diseases in Latin America is Chagas disease, with almost 20 million people being infected and 60 million others at risk of infection. In the cell infection by Trypanosoma cruzi, the first step is contact with the host cell by receptors and ligands on the membrane. It is known that lipids play an important role in the interaction process between pathogens and host cells with lipid rafts being highly specialized regions of the plasma membrane that are enriched in cholesterol and sphingolipids. We explored whether the treatment with methyl-beta-cyclodextrin alone or by adding Mevinolin, an inhibitor of cholesterol synthesis could deplete membrane cholesterol of the HEp2 cell and if this treatment could affect the trypomastigote infection into the host cell. These treatments led to a leakage of cholesterol, and concomitantly, PLAP enzyme and unidentified proteins resulting in a decrease of the invasion process. However, the GGTP enzyme was not liberated from the host cell membranes.
Assuntos
Fosfatase Alcalina/metabolismo , Colesterol/metabolismo , Trypanosoma cruzi/fisiologia , Animais , Anticolesterolemiantes/farmacologia , Linhagem Celular , Humanos , Lovastatina/farmacologia , Microdomínios da Membrana/fisiologia , Camundongos , Trypanosoma cruzi/enzimologia , beta-Ciclodextrinas/farmacologia , gama-Glutamiltransferase/metabolismoRESUMO
UNLABELLED: We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. CONCLUSION: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.
Assuntos
Carcinógenos/farmacologia , Carcinoma in Situ/induzido quimicamente , Fungicidas Industriais/toxicidade , Maneb/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Fenobarbital/farmacologia , Quercetina/farmacologia , Zineb/toxicidade , Alquilantes/toxicidade , Animais , Animais Recém-Nascidos , Carcinoma in Situ/patologia , Modelos Animais de Doenças , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Exposição Materna , Troca Materno-Fetal , Metilnitrosoureia/toxicidade , Neoplasias Pancreáticas/patologia , Gravidez , Ratos , Ratos WistarRESUMO
The purpose of this work was to analyze the effect of diets that contain several oils whose composition in fatty acids were different, on the kinetic parameters of the gamma-glutamyltranspeptidase (GGTP) and the lipoperoxidation of the epididymis because GGTP controls the level of the glutathione that is an molecule that regulates the level of oxidation protecting the maturation and survival of sperm in the lumen of the epididymis. The caput portion of the epididymis was chosen because the epithelium of this segment synthesizes GGTP. Weaned BALB-c mice were fed a commercial or semi-synthetic diet that contained 5% added olein. The mice were maintained on corn oil or fish oil diet for the first 4-8 months of age. The kinetic variables of the GGTP enzyme, analyzed by means of multiple regression analysis using dummy variables, showed that values were similar in olein and corn oil samples, whereas in samples from the fish oil fed group the enzyme behaved as that in animals maintained on commercial diets. Although there were no variations in maximum velocity (Vm) of the enzyme, the Km value, was greater (P < 0.0001) for the mice fed the olein and corn diets. These groups contained greater percentages of the monounsaturated fatty acids, palmitoleic (16:1 n-7) and oleic acid, 18:1 n-9. Similarly, the amount of lipid peroxidation was also greater in the olein and corn oil groups with respect to commercial and fish groups. The significant increment in Km of GGTP in the olein and corn groups was correlated with greater amount of monounsaturated fatty acids and lipid peroxidation in the epididymis. In conclusion, modifications of dietary lipid sources differentially modulated the epididymis tissue fatty acid profile, lipid peroxidation amounts, and the Km of GGTP. These effects may alter the metabolism of the natural substrate of GGTP, glutathione, a tripeptide with a powerful antioxidant activity, which is necessary in maintaining the oxidative state of the sperm microenvironment, thereby favoring maturation of the male gametes.
Assuntos
Gorduras na Dieta/farmacologia , Epididimo/enzimologia , Ácidos Graxos/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Maturação do Esperma/efeitos dos fármacos , gama-Glutamiltransferase/farmacocinética , Animais , Óleo de Milho/química , Gorduras na Dieta/administração & dosagem , Epididimo/metabolismo , Óleos de Peixe/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Maturação do Esperma/fisiologia , gama-Glutamiltransferase/efeitos dos fármacosRESUMO
The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22-25 and at 36-40 weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36-40 weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.
Assuntos
Carcinógenos , Dieta , Ácidos Graxos Insaturados/farmacologia , Lesões Pré-Cancerosas/prevenção & controle , Triazinas/toxicidade , Neoplasias Urológicas/prevenção & controle , Urotélio/patologia , Animais , Apoptose/efeitos dos fármacos , Testes de Carcinogenicidade , Cromatografia Gasosa , Feminino , Rim/patologia , Masculino , Mitose/efeitos dos fármacos , Índice Mitótico , Região Organizadora do Nucléolo/efeitos dos fármacos , Região Organizadora do Nucléolo/fisiologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Wistar , Bexiga Urinária/patologia , Neoplasias Urológicas/induzido quimicamente , Neoplasias Urológicas/patologiaRESUMO
INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.
Introducción: Según el concepto de cancerización de campo, existría alteración en la proliferación epitelial en áreas cercanas a tumores. Dicha proliferación podría ser modificada por lípidos dietarios. Objetivos: este estudio fue diseñado para analizar proliferación y apoptosis en epitelio lingual de ratones portadores de tumores salivalesinducidos por DMBA y alimentados con dietas a base de diferentes lípidos. Materiales y Métodos: Cuarenta y cinco días posteriores al destete, diez ratones BALB/c fueron asignados a dos dietas: maíz(M) y bacalao (B). Dos semanas después se inyectó DMBA en la zona submandibular. Los animales fueron sacrificados a ala 13º semana post-inyección. Muestras de lengua fueron fijadas en formal-etanl y procesadas inmunohistoquímicamente con marcadores de proliferación (Ki-67) y apoptosis. Mediante microscopia óptica, se efectuó un conteo de núcleos positivos a ambos marcadosres en un total de trecientas células en interfase, tanto en cara dorsal como ventral de lengua. Los resultados fueron analizados mediante Anális de Varianza y Test t. Resultados: La proliferación celular fue mayor en cara dorsal que en ventral (p> 0.001), sin diferencias por dieta. La apoptosis fue significativamentes mayor en ratones alimentados con B que M, en particular en cara dorsal (p<0.018). Conclusiones: Este estudio demuestra que la dieta B induce mayor apoptosis en ela epitelio lingua, sgiriendo un mecanismo defensivo de los tejidos ante el agente cancerígeno-tumoral.
Assuntos
Animais , Camundongos , Apoptose/efeitos dos fármacos , Carcinoma/patologia , Gorduras na Dieta/administração & dosagem , Neoplasias das Glândulas Salivares/patologia , Carcinógenos , Carcinoma/induzido quimicamente , Carcinoma/dietoterapia , Lesões Pré-Cancerosas/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Neoplasias das Glândulas Salivares/induzido quimicamente , Neoplasias das Glândulas Salivares/dietoterapia , Proliferação de Células/efeitos dos fármacosRESUMO
INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.(AU)
Introducción: Según el concepto de cancerización de campo, existría alteración en la proliferación epitelial en áreas cercanas a tumores. Dicha proliferación podría ser modificada por lípidos dietarios. Objetivos: este estudio fue diseñado para analizar proliferación y apoptosis en epitelio lingual de ratones portadores de tumores salivalesinducidos por DMBA y alimentados con dietas a base de diferentes lípidos. Materiales y Métodos: Cuarenta y cinco días posteriores al destete, diez ratones BALB/c fueron asignados a dos dietas: maíz(M) y bacalao (B). Dos semanas después se inyectó DMBA en la zona submandibular. Los animales fueron sacrificados a ala 13º semana post-inyección. Muestras de lengua fueron fijadas en formal-etanl y procesadas inmunohistoquímicamente con marcadores de proliferación (Ki-67) y apoptosis. Mediante microscopia óptica, se efectuó un conteo de núcleos positivos a ambos marcadosres en un total de trecientas células en interfase, tanto en cara dorsal como ventral de lengua. Los resultados fueron analizados mediante Anális de Varianza y Test t. Resultados: La proliferación celular fue mayor en cara dorsal que en ventral (p> 0.001), sin diferencias por dieta. La apoptosis fue significativamentes mayor en ratones alimentados con B que M, en particular en cara dorsal (p<0.018). Conclusiones: Este estudio demuestra que la dieta B induce mayor apoptosis en ela epitelio lingua, sgiriendo un mecanismo defensivo de los tejidos ante el agente cancerígeno-tumoral. (AU)
Assuntos
Animais , Camundongos , Apoptose/efeitos dos fármacos , Carcinoma/patologia , Gorduras na Dieta/administração & dosagem , Neoplasias das Glândulas Salivares/patologia , 9,10-Dimetil-1,2-benzantraceno , Carcinógenos , Carcinoma/induzido quimicamente , Carcinoma/dietoterapia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Lesões Pré-Cancerosas/patologia , Neoplasias das Glândulas Salivares/induzido quimicamente , Neoplasias das Glândulas Salivares/dietoterapiaRESUMO
Mice fed on semisynthetic formulas containing 15% of corn oil (CO), cod fish liver oil (FO), oleic acid (O) or a mixture of 46% of palmitic and 50% of stearic acids (PS) were treated with urethan during 18 weeks for lung tumor induction. Delayed-type hypersensitivity (DTH) assay, hemagglutination assay and the amount of lung nodes (alveolar adenocarcinomas) were recorded. Results showed significantly greater DTH in CO and FO with respect to O and PS feeding mice; the two last ones induced an essential fatty acid (EFA) deficiency (EFAD). In the O lot there was a non-significant diminution of the humoral response. EFAD animals exhibited a tendency to increase number of lung nodes in relation to CO and FO lots. Splenomegalia was recorded in FO lot. Confront between spleen weight and DTH showed a 72% correlation, suggesting an increase in cellular immunity as increasing unsaturation. It may be concluded that in this suitable model of tumorigenesis the manipulation of dietary lipids may be a strategy to modify the immune system response.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Essenciais/administração & dosagem , Hipersensibilidade Tardia , Imunidade Celular/efeitos dos fármacos , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Carcinógenos/toxicidade , Gorduras Insaturadas na Dieta/análise , Modelos Animais de Doenças , Ácidos Graxos Essenciais/deficiência , Feminino , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Uretana/toxicidade , Aumento de Peso/efeitos dos fármacosRESUMO
The effect of dietary quercetin (Q) was evaluated in rats treated with nitrosomethylurea (NMU). Pancreatic nodules and focal acinar cell hyperplasias were observed in groups treated with NMU (87%) and Q-NMU (100%). Although rats with dysplastic foci (27%) were found in the NMU-treated group, Q-NMU treatment resulted in a significantly higher number of rats with dysplastic foci (73%). Furthermore, carcinomas in situ (12%) and one microcarcinoma (4%) were found in these animals. Mitosis was significantly increased and apoptosis was diminished in focal acinar cell hyperplasias of the Q-NMU group. Our present results support a promoting and progressing effect of quercetin in the NMU model of rat pancreatic carcinogenesis.
Assuntos
Carcinógenos/toxicidade , Metilnitrosoureia/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Lesões Pré-Cancerosas/induzido quimicamente , Quercetina/toxicidade , Animais , Peso Corporal , Cocarcinogênese , Feminino , Masculino , Tamanho do Órgão , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/patologia , Gravidez , Ratos , Ratos WistarRESUMO
It is widely known that dietary lipids can modify the ability of different cancers to grow up and metastasize, especially mammary gland tumors. However, it is still unclear whether n-6 fatty acids behave as tumor promoters in this gland cell population. The effect of different nutritional polyunsaturated fatty acids (PUFAs) on tumor growth parameters of two transplantable murine mammary gland adenocarcinomas of low and high metastatic ability was tested on hosts fed diets with corn oil (CO) rich in 18:2n-6, evening primrose oil (EPO) containing 18:3n-6 (GLA) and a third formula supplemented with olein (O) 18:1n-9, which induces an essential fatty acid deficiency (EFAD). Tumor growth parameters were not adversely affected in the corn oil group with respect to stock-fed controls. Furthermore, metastatic spreading diminished in this group. EPO showed a moderate antitumor activity whereas the n-9-enriched diet showed no clear-cut effects. In both mammary gland tumors, n-6 fatty acid-rich lipids formulae, containing GLA and linoleic acid, were not tumor promoters. On the contrary, both exhibited anticancer activity.
Assuntos
Adenocarcinoma/secundário , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Neoplasias Mamárias Animais/patologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Animais , Carcinógenos , Gorduras Insaturadas na Dieta/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Feminino , Masculino , Neoplasias Mamárias Animais/induzido quimicamente , Neoplasias Mamárias Animais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Invasividade NeoplásicaRESUMO
Certain tumor growth parameters (GP) of two mesenchymal transplantable tumors maintained on C57BL/6J mice were characterized. Considering that many experimental, clinical and epidemiologic data have indicated that n-3 and n-6 essential fatty acids are nutrients which may delay the development as well as improve the course of cancer, GPs were evaluated on hosts fed on a semisynthetic formula containing 5% of corn oil (CO) or cod liver oil (CLO) and stock diet (C group). Although survival and latency time of tumor-bearing mice were shortened, other GP as percentage of successful implants were improved by both oils in sarcoma-bearing hosts, suggesting that n-3 and n-6 fatty acids might play a modulating role for the development of these tumors.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Linfoma/patologia , Sarcoma Experimental/patologia , Neoplasias Cutâneas/patologia , Animais , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Dieta , Ácidos Graxos Ômega-6 , Feminino , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Fibrossarcoma/ultraestrutura , Linfoma/tratamento farmacológico , Linfoma/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Sarcoma Experimental/tratamento farmacológico , Sarcoma Experimental/ultraestrutura , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/ultraestruturaRESUMO
Dynamins are GTPases which support receptor-mediated endocytosis and bind to several tyrosine kinase receptor-associated proteins known to mediate cell proliferation and differentiation. We have recently established that dynamin expression correlates with normal neuronal (Torre et al., J. Biol. Chem., 269 (1994) 32411-32417) and acinar pancreatic cell differentiation (Cook et al., Mol. Biol. Cell, 6 (1995) 405a). To begin to understand the role of dynamin in neoplastic pancreatic cell differentiation, we have followed the expression of this protein by immunohistochemistry during the development of pancreatic tumors in a mancozeb-nitrosomethylurea (NMU)-based carcinogenesis model recently developed in our laboratory (Monis and Valentich, Carcinogenesis, 14 (1993) 929-933). After a single intraperitoneal injection (50 mg/g body wt) of this carcinogen, rats fed with mancozeb develop pancreatic focal acinar hyperplasia (FACH), dysplastic foci (DYF) displaying acinar-like and ductular-like structures, and ductular-like carcinoma in situ (CIS). After histochemical staining using a monoclonal anti-dynamin antibody, high levels of this protein are consistently observed in well-differentiated acinar tumors (FACH). In contrast, dynamin immunoreactivity is almost undetectable in more advanced lesions showing a ductular-like phenotype (ductular-like DYF and CIS). This change in the expression pattern of dynamin during the progression of acinar into ductular-like DYF and CIS lesions correlates with recent findings from our laboratory showing a differential expression pattern for dynamin in pancreatic cells during embryonic development, with ductular-like precursor cells expressing low levels of this protein. Based upon these results, we conclude that more advanced ductular-like neoplastic cells induced by the carcinogen NMU in rat pancreas behave phenotypically like pancreatic precursor cells in their pattern of expression for dynamin.
Assuntos
Carcinógenos/toxicidade , Fungicidas Industriais/toxicidade , GTP Fosfo-Hidrolases/biossíntese , Maneb/toxicidade , Metilnitrosoureia/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/enzimologia , Zineb/toxicidade , Animais , Northern Blotting , Diferenciação Celular/efeitos dos fármacos , Dinaminas , Endocitose/fisiologia , Feminino , GTP Fosfo-Hidrolases/análise , GTP Fosfo-Hidrolases/fisiologia , Masculino , Neoplasias Pancreáticas/patologia , Ratos , Ratos Wistar , Receptores Proteína Tirosina Quinases/fisiologia , Transdução de Sinais/fisiologiaRESUMO
UNLABELLED: Rats were treated with a single i.p. injection of the carcinogen nitrosomethylurea (NMU, 50 mg/kg b.w.) at day three of age. The treatment induced hyperplastic and atypical acinar cell proliferation [focal acinar cell hyperplasia (FACH)]. In this investigation, NMU treated rats were fed AIN-76 diet containing mancozeb (MZ; 100 mg/kg diet), a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, which is an agricultural fungicide. EXPERIMENTAL DESIGN: Group one was treated with NMU plus MZ (MZ-NMU), group 2 received NMU alone (NMU), group 3 was fed MZ and saline injected (MZ-SAL) and group 4 was the saline injected control (SAL). Rats were killed at week 24 of age. In MZ-NMU group pancreas there were FACH, dysplastic foci (DYF) and carcinomas in situ (CIS). FACH were larger, coalescent and may show areas of undifferentiated cells (focus within focus). DYF contain proliferative acinar and ductular structures with loss of polarity but no malignant traits. CIS had medullary appearance or consisted of irregularly shaped acini and ducts in stromal framework. Cell had scant cytoplasm and large hyperchromatic, pleomorphic nuclei. DYF and CIS were not seen in MZ group pancreas. The MZ-NMU group had increased mitotic index and greater number of apoptotic cells. There was no pathologic change in MZ-SAL group. Our data indicated that MZ did not cause pancreatic cell proliferation in normal rats whereas it had distinct promoting and progressor effects on NMU initiated pancreatic cells. Thus, a two-stage protocol of pancreatic carcinogenesis was achieved. It is suggested that the NMU protocol may be useful for testing promoter, progressor or inhibitory effect of chemical and physical agents on cell proliferation and transformation of rat pancreas.
Assuntos
Carcinógenos/toxicidade , Carcinoma in Situ/induzido quimicamente , Fungicidas Industriais/toxicidade , Maneb/toxicidade , Metilnitrosoureia/toxicidade , Pâncreas/patologia , Neoplasias Pancreáticas/induzido quimicamente , Zineb/toxicidade , Animais , Animais Recém-Nascidos , Carcinoma in Situ/patologia , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/ultraestrutura , Feminino , Hiperplasia , Lactação , Troca Materno-Fetal , Pâncreas/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Gravidez , Ratos , Ratos Wistar , Valores de ReferênciaRESUMO
The present report is a study of the effect of the carcinogen nitrosomethylurea (NMU) on pancreas of rats receiving during lifetime a lipid-poor diet, that is essential fatty acid deficient or control diets. Rats fed a commercial stock chow were mated. At day 10 of pregnancy, dams were divided into three groups, that were respectively supplied with the commercial chow, the essential fatty acid deficient or the sufficient diet. Each litter was separated at random in two groups that received at day one of life one intraperitoneal injection of NMU (50 mg/kg b.w.) or saline. After weaning, they were maintained for life with the diet that was supplied to their mothers. The pancreas of NMU-treated rats presented diffuse proliferative changes, focal acinar cell hyperplasias (FACH), and focal hepatocyte-like metaplasia (FHLCM). FACH were expansive presumably preneoplastic growths, showing abnormal differentiation. The number of NMU-treated rats bearing FACH and FHLCM did not significantly differ in the three nutritional conditions.
Assuntos
Metilnitrosoureia/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Essenciais/administração & dosagem , Feminino , Hiperplasia , Metaplasia , Pâncreas/patologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Gravidez , Ratos , Ratos EndogâmicosAssuntos
Metilnitrosoureia/farmacologia , Pâncreas/efeitos dos fármacos , Tiram/farmacologia , gama-Glutamiltransferase/biossíntese , Administração Oral , Peso Corporal/efeitos dos fármacos , Dieta , Indução Enzimática/efeitos dos fármacos , Inativação Metabólica , Metilnitrosoureia/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/enzimologia , Pâncreas/patologia , Tiram/administração & dosagemRESUMO
The effect of essential fatty acid deficiency and nitrosomethylurea treatment on postnatal levels of pancreatic gamma-glutamyltranspeptidase was studied. A significant increase of gamma-glutamyltranspeptidase activity and changes in fatty acid composition were observed in essential fatty acid deficient rats, from the 14th day of life on. Pancreatic gamma-glutamyltranspeptidase of nitrosomethylurea injected rats in essential fatty acid deficiency and controls was significantly diminished at the 30th day, with no significant differences in both nutritional conditions. The results indicated: 1. Concomitant changes in gamma-glutamyltranspeptidase activity and fatty acid composition of rat pancreas in essential fatty acid deficiency, 2. A significant reduction of pancreatic gamma-glutamyltranspeptidase activity following a single intraperitoneal injection of nitrosomethylurea at day one of life and 3. No interacting effects of essential fatty acid deficiency and nitrosomethylurea on gamma-glutamyltranspeptidase activity of rat pancreas.
Assuntos
Ácidos Graxos Essenciais/deficiência , Metilnitrosoureia/farmacologia , Pâncreas/enzimologia , gama-Glutamiltransferase/metabolismo , Animais , Animais Recém-Nascidos , Dieta , Ácidos Graxos/análise , Feminino , Masculino , Pâncreas/química , Ratos , Ratos EndogâmicosRESUMO
Microspectrophotometric DNA measurements in exocrine pancreas of essential fatty acid-deficient (EFAD) and EFA-sufficient (EFAS) rats which received a single intraperitoneal injection of the carcinogen nitrosomethylurea (NMU) or saline (SAL) was the subject of the present report. The DNA content of acinar pancreatic cells of SAL-injected EFAD and EFAS rats was diploid. NMU-induced pancreatic focal acinar cell hyperplasia (FACH) had one main cell population with a diploid content, whereas in the intervening parenchyma there were diploid and tetraploid cells. The number of tetraploid cells was smaller in EFAD rat pancreas than in EFAS indicating a diet dependent effect. NMU-induced FACH had a diploid distribution pattern indicating that cells are in a G1, quiescent phase, contrasting with AZA-induced similar lesions which showed an abnormal ploidy. It remains to be established whether DNA phenotypic traits of NMU and AZA induced FACH reflect the neoplastic potentials of both types of lesions. The decreased number of tetraploid cells in EFAD rat pancreas is in keeping with data indicating a promoting effect of the EFA linoleic and arachidonic acids on growth rate of certain cell populations in vitro.