Effects of aloe arborescens ingestion on azoxymethane-induced intestinal carcinogenesis and hematological and biochemical parameters of male F344 rats.

We examined the modifying effect of freeze-dried whole-leaf Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japan; designated as 'ALOE') on azoxymethane (AOM)-induced intestinal carcinogenesis in rats. Male F344 rats (4 weeks old) were fed basal diet or experimental diet containing 0.2% or 1% ALOE for 28 weeks. Starting two weeks later, the animals received subcutaneous injections of AOM once weekly for 10 weeks. The incidence of colorectal adenocarcinomas in the 0.2% (but not 1%) ALOE group showed a strong tendency for decrease (p = 0.056) from the control group. Further, the adenocarcinoma incidence in the entire intestine (small and large intestines) in the 0.2% ALOE group was significantly (p = 0.024) decreased compared to the control value. However, there were no significant differences in tumor multiplicities of colorectal or entire intestines among the 3 groups. In addition, we also studied the safety of long-term ingestion of ALOE as a health food or natural thickening stabilizer. Rats were fed the basal diet or 1% ALOE diet for 35 weeks without AOM treatment. Feeding with 1% ALOE did not affect most hematological and serum biochemical parameters in the rats. These results indicate that a low level of ALOE ingestion might have a mild suppressive effect on intestinal tumor growth without harmful side effects.

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.

Efecto de la sacarina de sodio en el intestino grueso del raton / Sodium saccharin effect in the mice large intestine

Se ha comprobado que la sacarina de sodio es un promotor tumoral del epitelio de la vegija de rata, propiedad no demostrada en el ser humano y actualmente discutida. En este trabajo se describen las alteraciones que produce este edulcorante en el epitelio del colon descendente de ratones cepa C3H, cuando es adicional al alimento en bajas dosis. Se muestra por microscopia electrónica de transmisión, que la sacarina de sodio produce en las células absortivas del epitelio del colon un pleomorfismo microvellositario constituido por microvellosidades de diferente forma, longitud, diámetro y curvatura.

Ossification of the N-methyl-N'-nitro-N-nitrosoguanidine-induced small intestine adenocarcinomas in rats

Eighty rats out of 233 developed malignant tumors in the stomach and small intestine by administration of 100 micrograms/ml N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 28 weeks. Fifteen lesions (30%) among the 50 small intestinal carcinomas showed ossification in the tumor, while none in the sarcomas (12 lesions) or gastric adenocarcinomas (59 lesions) showed ossification. Multifocal heterotopic bone formation was found within stroma in close approximation to the neoplastic glands. The islands of bone trabeculae were covered by osteoblast-like cells, and abundant fibroblasts in loose stroma gathered around the bony islands which enclosed osteocytes in lacunae. Neither osteoclast nor cartilage was identified. In 5 cases, ossification was extensive, which comprised the major portion of the stroma. In contrast, intraluminal calcification without ossified foci were occasionally seen in the gastric carcinoma. Ossification of the intestinal tumors correlated to the degree of mucin content (p<0.05, chi square with Yates' correction), degree of neutrophilic infiltration (p<0.05), and size of the tumor (p<0.1). (The average size of the ossified tumor was 21.5 +/- 4.0 mm, while that of nonossified tumors was 12.5 +/- 1.9 mm). The degree of tumoral necrosis, desmoplasia or depth of invasion did not seem to be related to the ossification of the tumor. The ossification rate of this experimental model was much higher than in human cases. Various histologic alterations, such as mucin leakage, inflammatory cell infiltration, necrosis and/or fibrosis, which might be caused by continuous stimulation of the strong carcinogen, may play some role in the ossification of experimental tumors.

Neoplastic Paneth cells in the experimental murine carcinoma of the small intestine

The purpose of this study is to elucidate the participation of Paneth cells in experimentally induced adenocarcinoma of the intestine. The rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water ad libitum at a concentration of 100 micrograms/ml for 28 weeks. They were sacrificed 12 weeks after the last MNNG administration. A number of tumor cells containing large eosinophilic granules in their supranuclear cytoplasm (Paneth cells) were observed in about 20% of the experimentally induced adenocarcinoma of the small intestine. The granules were stained positively with Lendrum, periodic acid-Schiff, Masson's trichrome, and Mallory's phosphotungstic acid hematoxylin. Ultrastructurally, the granules were round, osmiophilic, and relatively even in size. We compared the morphologic features of the Paneth cell-containing small intestinal adenocarcinomas (Group I) with those without Paneth cells (Group II). Group I was distinguished from Group II by its better differentiation, larger tumor size and lower incidence of calcification. Although Paneth cells are extremely rare in human gastrointestinal carcinomas, twenty percent of MNNG-induced intestinal carcinomas harbor Paneth cells. The neoplastic Paneth cells in experimental carcinomas may differentiate from uncommitted cells in the deeper portion of the crypt.

Atividade de xantina-oxidase na carcinogênese induzida pela 1.2-dimetil-hidrazina / Xantina-Oxidase activity in carcinogenesis induced by 1,2-dimethylhydrazine

A 1,2-dimetil-hidrazina (DMH) induz a formaçäo de tumores no intestino de ratos após aplicaçöes semanais durante 20 semanas. As atividades de xantina-oxidase (XO) e xantina-desidrogenase (XD) variam de acordo com a distância ao longo do intestino. Nos animais injetados com DMH verifiou-se uma diminuiçäo da atividade enzimática exatamente na porçäo onde ocorre maior incidência tumoral. Anotou-se, também, um aumento da atividade XD em soro sangüíneo de ratos tratados com DMH