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      Effect of ethanol consumption on colon cancer in an experimental model Translated title: Efecto de la ingesta de etanol en un modelo experimental de cáncer de colon

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          Abstract

          Aims: the present study was designed to examine the effect of an ethanol supplement on experimental colon carcinogenesis. Material and methods: one hundred and ten 10-week-old Sprague-Dawley rats were divided into five groups: group A (20 rats) received no treatment. Group B (20 rats) received a supplement of ethanol at 1.23 g/kg of body weight per day added to their drinking water for 24 weeks. Group C (30 rats) received 18 weekly doses of dimethylhydrazine (DMH) at 21 mg/kg of body weight from the beginning of the study. Group D (20 rats) received ethylen-diamin-tetracetic acid (EDTA) solution only for 18 weeks. Group E (20 rats) received ethanol at the same dose as group B plus DMH injections at the same dose as the rats in group C from the beginning of the study. All experimental animals were sacrified after 25-27 weeks. Results: no significant differences in the number of rats that developed tumors, number of tumor-free animals, and number of tumors per rat, as well as in macro-microscopic tumoral findings were observed for animals in group C compared to animals in group E. Conclusions: we concluded that the addition of an ethanol supplement does not modify colorectal carcinogenesis using a dynamic model of tumor induction with DMH.

          Translated abstract

          Objetivos: el presente trabajo experimental fue diseñado para examinar el efecto de la adición de un suplemento de etanol oral en ratas, en la aparición y desarrollo de la carcinogénesis colónica. Material y métodos: se utilizaron un total de ciento diez ratas de la raza "Sprague-Dawley" de 10 semanas de vida, que se dividieron en 5 grupos: grupo A (20 ratas), sin tratamiento. Grupo B (20 ratas), con adición de etanol a la dosis de 1,23 g/kg peso al día, añadido al agua de bebida, durante 24 semanas. Grupo C (30 ratas), tratadas con 18 dosis semanales de dimetilhidracina (DMH) a la dosis de 21 mg/kg peso, cada una, desde la semana 10 de vida. Grupo D (20 ratas), tratadas únicamente con solución de ácido etilen-diamino-tetracético (EDTA), durante 18 semanas. Grupo E (20 ratas), tratadas con etanol a la misma dosis que las ratas del grupo B y las mismas inyecciones de DMH que las ratas del grupo C, administradas ambas de forma concomitante, desde la semana 10 de vida. Todas las ratas fueron sacrificadas entre las 25-27 semanas, del comienzo del estudio. Se estudió la incidencia de tumores colorrectales y su localización, así como los hallazgos anátomo-patológicos comparados entre grupos. Resultados: no se observaron diferencias significativas, ni en el número de ratas que desarrollaron tumores de colon, ni en el número de animales libres de tumor, ni en el número de tumores por rata, ni en los hallazgos macro-microscópicos de los tumores entre los animales del grupo C, con respecto a los del grupo E. Conclusiones: la adición de un suplemento de etanol a la dieta, en la dosis y tiempo establecidos, no modificó la producción de carcinogénesis colónica en ratas, usando un modelo dinámico de administración concomitante de inducción tumoral con DMH.

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          Most cited references44

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          Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence.

          Whether colon cancer risk can be modified by a diet rich in vegetables, grains, and fruit, and, if so, whether the protective factor is dietary fiber or other biologically active components correlated with a high-fiber diet are questions of active research interest. Because studies on diet are susceptible to bias from a number of sources, in this review we evaluated the adequacy of study methodology as well as study results to clarify how much protection, if any, is conferred by a high-fiber diet. The review consisted of an aggregate assessment of the strength of evidence from 37 observational epidemiologic studies as well as meta-analyses of data from 16 of the 23 case-control studies. Both types of analyses revealed that the majority of studies gave support for a protective effect associated with fiber-rich diets; an estimated combined odds ratio (OR) of 0.57 (95% confidence interval = 0.50, 0.64) was obtained when the highest and lowest quantiles of intake were compared. Risk estimates based on vegetable consumption (OR = 0.48) were only slightly more convincing than those based on an estimate of fiber intake (OR = 0.58), but the data do not permit discrimination between effects due to fiber and nonfiber effects due to vegetables.
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            Possible role of acetaldehyde in ethanol-related rectal cocarcinogenesis in the rat.

            Prospective epidemiologic studies have reported an increased risk of rectal cancer following chronic ethanol ingestion. The effect of ethanol on chemically induced colorectal carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic ethanol administration on acetoxymethylmethylnitrosamine-induced rectal cancer and the possible role of acetaldehyde in this process were investigated. Chronic ethanol administration resulted in an earlier occurrence of rectal tumors in this animal model. Because the concomitant administration of cyanamide, a potent acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of tumors, acetaldehyde could be involved in the ethanol-associated carcinogenesis. To measure colonic acetaldehyde, 12 chronically ethanol-fed and control rats received an acute dose of ethanol (2.5 g/kg body wt). The mucosal concentration of acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic ethanol feeding. Furthermore, 6 germ-free rats had significantly lower acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg protein-1, p less than 0.05). The data show that chronic ethanol ingestion accelerates chemically induced rectal carcinogenesis and raise the possibility that acetaldehyde probably generated through bacterial ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour carcinogenesis.
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              Calcium inhibits colon carcinogenesis in an experimental model in the rat.

              Different dietary factors can affect colorectal cancer incidence. However, the effect of increased levels of dietary calcium on neoplasms is unclear. The present study was designed to examine the effect of a low calcium supplement on experimental colon carcinogenesis induced by parenteral administration of dimethylhydrazine (DMH). One hundred and twenty 10-week-old Sprague-Dawley rats were divided into five groups of equal sex distribution. The 10 rats in group A (control group) received no treatment; the 30 rats in group B (DMH group) were injected subcutaneously with 18 weekly doses of 21 mg/kg DMH; the 20 rats in group C (EDTA control group) received EDTA solution only; the 30 rats in group D (calcium group) received calcium at 3.2 g/l by adding calcium lactate to the drinking water from the start until the conclusion of the experiment; and the 30 rats in group E (DMH + calcium group) received oral calcium supplements at the same dose as the rats in group D (calcium group) and the same DMH injections as the rats in group B (DMH group). The rats were sacrificed at 25-34 weeks. In group E, we observed a significant diminution in the number of tumours (P = 0.01); an increase in the number of tumour-free animals (P = 0.006); a change in tumour location towards the distal colon (P < 0.025); more adenomas (P = 0.02); and a diminution of adenocarcinomas and mucinous carcinomas, although this was not significant. We conclude that a low dietary calcium supplement in rats inhibits colon cancer carcinogenesis induced by DMH, and changes tumour location towards the distal colon.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                diges
                Revista Española de Enfermedades Digestivas
                Rev. esp. enferm. dig.
                Sociedad Española de Patología Digestiva (Madrid )
                1130-0108
                February 2005
                : 97
                : 2
                : 87-96
                Affiliations
                [1 ] Hospital Grande Covián Spain
                [2 ] Universidad de Oviedo Spain
                [3 ] University of Lleida Spain
                Article
                S1130-01082005000200003
                10.4321/s1130-01082005000200003
                4ea155ea-687a-4470-a1c0-7504dd3d801f

                http://creativecommons.org/licenses/by/4.0/

                History
                Categories
                GASTROENTEROLOGY & HEPATOLOGY

                Gastroenterology & Hepatology
                Alcohol,Cancer,Carcinogenesis,Colon,Dimethylhydrazine,Ethanol,Neoplasm,Tumors,Cáncer,Carcinogénesis,Dimetilhidracina,Etanol,Neoplasia,Tumores

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