RESUMO
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.
Assuntos
DNA/metabolismo , Ácidos Graxos Essenciais/deficiência , Metilnitrosoureia/farmacologia , Pâncreas/metabolismo , Animais , Feminino , Microespectrofotometria , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Chick embryos injected with lambda-carrageenan prior to incubation and studied with light microscopy at 48 hours of development presented various anomalies. Lack of closure at different levels of the neural tube was one of the lesions most frequently seen. Rachischisis and craniorachischisis were commonly associated with various degrees of hyperplasia of the neural tube wall. Diverse patterns of neural hyperplasia ranged from total occlusion of the neural tube to localized thickening of lateral walls leading to a typical "hourglass" appearance of the ependymal lumen. Multiple septa and cavitations of the neural tube lumen were also recorded. Cephalic and/or trunk duplication of the body as well as disorganization of notochord and somites were frequently associated with rachischisis and areas of necrosis or pyknosis of neural tissue. Neural crest cells, which are normally present in paraneural areas at the stages studied, were not encountered in the carrageenan-injected embryos. These areas were frequently occupied by hyperplastic ectodermic folds. Similarity of present findings on carrageenan-treated embryos with the anomalies induced by selective destruction or impairment of migration of neural crest cells suggests that involvement of this cell population may have a role in the causation of the anomalies observed.