RESUMEN
Colon cancer is known to be heritable in humans, but the opportunity to investigate the genetic epidemiology of cancer in nonhuman primates has been limited by the size of available populations. The cotton-top tamarin (Saguinus oedipus) colony at the Oak Ridge Associated Universities (ORAU) Marmoset Research Center is a large population with a high rate of spontaneous colon cancer that has been monitored over several years, thus allowing investigation of the genetic basis for colon cancer in this colony. The presence of colon cancer at death was scored in 392 necropsies at the colony. Genealogical and demographic data for these animals were obtained from colony records. The heritability of the liability to colon cancer was estimated using maximum-likelihood-based pedigree analyses after evaluating the effects of gender, origin (wild-born or laboratory-born), and age at death on cancer experience. Cancer rates were not significantly different between males and females or between wild- and laboratory-born animals. Differences in age at death were also statistically insignificant for both laboratory- and wild-born animals. The heritability estimate for the liability to contract colon cancer is 17% for the ORAU cotton-top tamarins. This heritability estimate is not significantly different from zero, indicating no evidence for heritable variation in cancer experience in this population. If genetic factors affect cotton-top tamarin colon cancer, they are fixed or nearly fixed in this population.
Asunto(s)
Neoplasias del Colon/genética , Modelos Genéticos , Saguinus/genética , Animales , Neoplasias del Colon/epidemiología , Femenino , Incidencia , Masculino , Factores SexualesRESUMEN
Spontaneous colitis in CTT's presents cytological characteristics similar to chronic ulcerative colitis in humans, e.g. inflammatory cell infiltrate and crypt abscesses. To better characterize CTT colitis as a potential model for human inflammatory bowel disease (IBD), inflammatory mediators identified in colonic tissue of human IBD patients and/or experimental colitis models were assayed. Inflammatory mediator changes in plasma and colon from tamarins with acute (n = 10) and chronic (n = 10) colitis (by mucosal biopsy) were assayed by RIAs. Similar inflammatory mediators were found in the CTT's with acute colitis. In the plasma, PAF and PGE2 levels were lower in acute colitis CTT's, no LTB4 was detected, and histamine levels were not different from chronic colitic animals. In the colon, myeloperoxidase and interleukin-1 beta were significantly higher in acute colitis, PGE2 and LTB4 were higher but not significantly, and PAF was not different from chronic CTT's. These data suggest that a combination of events are occurring in the pathogenesis of tamarin colitis that involves some of the same mediators that are found in the human disease and in other experimental models. The importance of these findings to human IBD remains for further investigation; however, the spontaneous primate model offers an exciting approximation of the disease development and merits further investigation for understanding the pathogenesis of human IBD as well as to aid in development of targeted therapeutics.
Asunto(s)
Colitis/metabolismo , Saguinus , Enfermedad Aguda , Animales , Enfermedad Crónica , Colitis/patología , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Histamina/metabolismo , Interleucina-1/metabolismo , Leucotrieno B4/metabolismo , Peroxidasa/metabolismo , Factor de Activación Plaquetaria/metabolismoRESUMEN
The future study of colon disease in captive callitrichid colonies may require manipulation of diets. The limited knowledge of the nutritional requirements for these species and the varied diets and supplementations fed to these animals in various colonies suggest the importance of testing the palatability and acceptability of diets for these primates. Individually housed cotton-top tamarins (Saguinus oedipus) were given either the regular Oak Ridge Associated Universities (ORAU) diet (monkey chow slurry, canned diet and supplements), a similar slurry using an experimental natural ingredient diet plus supplements, or the experimental diet without supplements. Neither dry food consumption, body weight, fecal output, nor the histological evaluation of the colons were affected by these diets. Daily intake of protein and calories were higher than previously reported estimates for the species. These results demonstrate that a natural ingredient non-sweetened pelleted diet is palatable for cotton-top tamarins for a period of 3.5 months, however, further testing over longer time periods is necessary. The nonnutritional (e.g. psychological) advantages of providing a highly diverse diet to primates housed in a relatively monotonous environment should be considered before adopting such a diet for an entire colony.
Asunto(s)
Alimentación Animal , Callitrichinae/metabolismo , Dieta , Saguinus/metabolismo , Animales , Biopsia/veterinaria , Peso Corporal , Colon/anatomía & histología , Ingestión de Alimentos , Heces , Saguinus/anatomía & histologíaRESUMEN
Endoscopic visualization and biopsy have been performed under anesthesia in more than 65 tamarins and marmosets to study the pathogenesis of colitis and cancer of the colon. This procedure allows examination of the large bowel from the anus to the cecum and has been repeated at 2-6 month intervals with few complications. However, care must be exercised not to perforate the colon. Successful use of this technique will permit study of the pathogenesis of colonic diseases throughout the life of the animal and should provide cause-effect information about colitis and colon cancer in tamarins that may apply to the human diseases.
Asunto(s)
Callitrichinae/anatomía & histología , Colon/anatomía & histología , Animales , Biopsia/veterinaria , Callithrix , Colitis/patología , Colitis/veterinaria , Colon/patología , Neoplasias del Colon/patología , Neoplasias del Colon/veterinaria , Colonoscopía/veterinaria , Saguinus , Especificidad de la EspecieAsunto(s)
Enfermedades de los Animales/patología , Callitrichinae , Neoplasias del Colon/veterinaria , Saguinus , Factores de Edad , Enfermedades de los Animales/genética , Animales , Peso Corporal , Callitrichinae/genética , Neoplasias del Colon/genética , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Femenino , Masculino , Metástasis de la Neoplasia , Linaje , Saguinus/genética , Factores SexualesRESUMEN
This study was designed to determine the effects of four well-characterized dietary brans on large bowel tumorigenesis induced in mice with 1,2-dimethylhydrazine (DMH). Eight-week-old barrier-derived male Balb/c mice were fed a semisynthetic diet with 20% bran added (either corn, soybean, soft winter wheat, or hard spring wheat) or a no-fiber-added control diet. Half of each group was given DMH (20 mg/kg body weight/week, subcutaneously for 10 weeks) beginning at 11 weeks of age. Surviving mice were killed 40 weeks after the first DMH injection. Tumors were not found in mice not subjected to DMH. In DMH-treated mice, tumors were found almost exclusively in the distal colon. Tumor incidences were as follows: controls, 11%; soybean group, 44%; soft winter wheat group, 48%; hard spring wheat group, 58%; and corn group, 72%. Tumors per tumor-bearing mouse ranged from 1.4 to 1.6, except in the corn group, which had 2.1. A positive correlation was found between percentage of neutral detergent fiber in the brans and tumor incidences but not between the individual components of cellulose, hemicellulose, or lignin. The enhancement of DMH-induced large bowel tumorigenesis by all four bran types may reflect a species and/or mouse strain effect that is bran-source related. These data emphasize the importance of using well-defined bran in all "fiber" studies.