Effects of high molybdenum intake on 1.2 - dimethylhydrazine-induced intestinal tumors in rats

Wistar male rats, 3 months of age were given ad-libitum a nutritionally adequate diet and demineralized drinking water. The Molybdenum (Mo) and Tungsten (W) were provided in the drinking water at 200 ppm concentration. Intestinal tumors were induced by 1,2-dimethylhydrazine (DMH) given subcutaneously as 16 weekly doses at 20 mg/kg body weight. Mo in the form of (NH4)6 Mo7O24 4H2O or W in the form of (Na2WO4) were provided in the drinking water two months before the first DMH treatment and were continued during 4 months more until the last DMH treatment. Three months after the last carcinogen injection, all animals were sacrificed and examined for intestinal tumors. The number, size and location of the tumors were recorded and the pathology was examined. The addition of Mo to the drinking water induced an increase of hepatic Mo content. At the end of the second month, the hepatic content of Mo was 5.61 ppm, compared with control and W groups (2.18 and 0.96 ppm, respectively). A significantly lower incidence of tumors was observed in the Mo group (47), compared with the control group given DMH alone (105) and W group (113). On the other hand, the Mo group showed a significant decrease in the numbers of multiple tumors per rat.

Effects of high molybdenum intake on 1,2-dimethylhydrazine-induced intestinal tumors in rats.

Wistar male rats, 3 months of age were given ad-libitum a nutritionally adequate diet and demineralized drinking water. The Molybdenum (Mo) and Tungsten (W) were provided in the drinking water at 200 ppm concentration. Intestinal tumors were induced by 1,2-dimethylhydrazine (DMH) given subcutaneously as 16 weekly doses at 20 mg/kg body weight. Mo in the form of (NH4)6 Mo7O24 4H2O or W in the form of (Na2WO4) were provided in the drinking water two months before the first DMH treatment and were continued during 4 months more until the last DMH treatment. Three months after the last carcinogen injection, all animals were sacrificed and examined for intestinal tumors. The number, size and location of the tumors were recorded and the pathology was examined. The addition of Mo to the drinking water induced an increase of hepatic Mo content. At the end of the second month, the hepatic content of Mo was 5.61 ppm, compared with control and W groups (2.18 and 0.96 ppm, respectively). A significantly lower incidence of tumors was observed in the Mo group (47), compared with the control group given DMH alone (105) and W group (113). On the other hand, the Mo group showed a significant decrease in the numbers of multiple tumors per rat.

Glomerular lesions in renal biopsies of Saimiri boliviensis (primate) examined by light and electron microscopy and immunohistochemistry.

In order to determine the existence of glomerular lesions in Saimiri boliviensis, renal biopsies were performed in 20 clinically healthy animals of similar age and both sexes. Biopsies were obtained by laparotomy with a Tru-Cut biopsy needle. Mesangioproliferative glomerulonephritis characterized by an increased number of mesangial cells and increased mesangial matrix was present in 35% of the animals. Proliferative glomerulonephritis characterized by increased numbers of epithelial and endothelial cells with narrowed capillary lumen, and membranous glomerulonephritis characterized by diffuse thickening, wrinkling, and occasional lamellation of basement membranes, were present in 15% of the samples. Ultrastructural features included increased mesangial matrix, fusion of the visceral epithelial foot processes, thickened glomerular basement membranes, and incipient lamellation. Immunohistochemical examination revealed granular deposits of immunoglobulin M in the cytoplasm of mesangial cells and in the mesangial matrix in 50% of the samples.

Failure to induce tumors in the large intestine of Capuchin mokeys (Cebus apella) by using 1,2-dimethylhydrazine.

The purpose of this study was to produce tumors in the large intestine of Capuchin Monkeys (Cebus apella) by the administration of the colonotropic carcinogen 1,2-dimethylhydrazine (DMH). The subjects were 12 monkeys, all males, age 30 months, with a mean weight of 2.858 kg. The DMH was administered subcutaneously to six of the monkeys at a dosage of 25 mg/kg of body weight once a week for 16 weeks; control monkeys received an equivalent volume of the stock solution without DMH. Twenty months after administration of the first dose, the animals were sacrificed. None of the monkeys showed intestinal tumors. Samples of the gastrointestinal tract were removed, fixed, and stained according to standard histological techniques. Histological changes were seen in all of the DMH-treated animals; these consisted of glandular hyperplasia and hyperplasia of the epithelium overlying the lymphoid nodules. In addition, foci of dysplasia were found in three of the animals. Our results suggest that the DMH induced pre-neoplastic changes, characterized by hyperplasia and dysplasia, in the mucosa of the large intestine.

[Histological and histochemical study of hyperplastic and dysplastic lesions of the large intestine in Cebus Apella (primate) treated with 1,2-dimethylhydrazine]. / Estudio histológico e histoquímico de lesiones hiperplásicas y displásicas del intestino grueso en Cebus apella (primate) tratado con 1,2-dimetilhidrazina.

The main objective of this study was to assess the histological changes of colon ephitelium in Cebus apella induced by 1,2-dimethylhydrazine (DMH) administration. Twelve monkeys, males, (aged x: 30 months) with an average body weight of 2,800 g were utilized. The DMH was injected subcutaneously at 25 mg/kg and continued once a week for 16 weeks. The body weight was assessed once a week during the first 4 months and every 30 days until the end of the experience. Histological changes of intestinal ephitelium and mucins were assessed at the end of the experience in specimens sectioned at 5 microns, stained with Haematoxylin and Eosin, PAS and Alcian blue pH 2.5. The histological and histochemical study permitted to characterize the normal morphology, as well as the mucins characteristics in the three regions: caecum, transverse colon and distal colon. The histological changes in the DMH treated animals were hyperplasia, dysplasia and mucins decreasing. The hyperplastic changes were localizated in glandular crypts, and in the epithelio located over the lymphoid nodules. The dysplastic crypts were observed in the transverse colon and in the last portion of distal colon. These lesions were located in the upper portion as well as the bottom of the mucosa. A decrease of neutral and acids mucopolysaccharides were observed in the crypts. The results of this study suggest that the DMH induced hyperplastic changes in the crypts and in the epithelium located over the lymphoid nodules and dysplastic focus, as well as a decrease of neutral and acids mucopolysaccharides.

Spontaneous hepatocellular carcinoma in Saimiri boliviensis.

Hepatocellular carcinomas are rare in nonhuman primates. In this study we found the first naturally occurring hepatocellular carcinoma in a Squirrel Monkey (Saimiri boliviensis) of at least 24 years of age. In the necropsy, the liver was cirrhotic and contained multiple tumorous nodules, which varied in diameter from 3 to 15 mm. The lungs also contained small neoplastic masses. In the histological study, samples of liver, lungs, and other organs were taken and fixed in 10% buffered formalin, embedded in paraffin, cut at 5 microns, and colored with hematoxylin and eosin. The histological study of the liver permitted the detection of multiple masses of neoplastic liver cells in a closely packed trabecular configuration surrounded by a well-developed capillary basement membrane. Cirrhotic changes also were observed in the liver. The histological study of the lung confirmed the metastasis of the hepatocellular carcinoma. Metastasis was not found in other organs.