Asunto(s)
Alelos , ADN Satélite/genética , Antígenos Comunes de Leucocito/genética , Animales , Secuencia de Bases , Cartilla de ADN/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Ratas , Ratas Endogámicas , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Female virgin BDII/Han rats develop spontaneous endometrial carcinoma (EC) in incidences up to 90%. Our objective was to determine whether lifelong administration of the progestin melengestrol acetate (MGA) would suppress those tumors. Four groups of 20 rats aged 24-28 days were employed Group I animals were untreated controls. Groups II, III, and IV were fed 0.1, 0.2, and 0.4 mg MGA/kg daily in their diet during their lifetimes. All treated groups were free from EC during their lifetimes with an increased lifespan up to 30%. The controls, in contrast, had an EC incidence of 85%. Histologically, with one exception all tumors were classified as adenocarcinoma. While most of the control rats died from EC, nearly all animals of groups II and III died from age-related diseases. Rats in group IV showed side effects due to the glucocorticoid properties of MGA. Besides alopecia and obesity an acceleration of chronic progressive nephrosis was observed. The study establishes the validity of the prophylactic approach to spontaneous hormone-dependent cancers in a rat tumor model.
Asunto(s)
Adenocarcinoma/prevención & control , Neoplasias Endometriales/prevención & control , Acetato de Melengestrol/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Estro/efectos de los fármacos , Femenino , Acetato de Melengestrol/administración & dosificación , Ovario/efectos de los fármacos , Ratas , Organismos Libres de Patógenos Específicos , Útero/efectos de los fármacosRESUMEN
Food consumption, development of body weight, lifespan and incidence of spontaneous diseases and tumours were investigated in 3 groups of 96 male Han:SPRD rats each maintained in a longevity study from weaning up to their natural death. All rats were fed a commercial cereal-based diet. One group received food ad libitum and was used as control group. Access to the diet was controlled in the other two groups by means of an automatic timer. The rats of one of the latter groups were fed nocturnally (4 x 42 min daily during the dark period) and those of the other adiurnally (4 x 42 min daily, each two times during dark and light period). Time-scheduled feeding caused an evident food restriction compared with the food consumption of the rats fed ad libitum. This food restriction, however, was significantly more pronounced in the younger animals during the first weeks after weaning than in the older rats. The body weight development corresponded to the feed intake. In animals subjected to food restriction the weight remained below that of rats fed ad libitum during all age periods. Furthermore, time-scheduled feeding caused an important increase of the mean life expectancy and a reduction in the incidences of chronic nephropathy and purulent and chronic forms of prostatitis. Only a slight effect of controlled feeding was observed on the incidence of alveolar lipoproteinosis. Time-scheduled feeding did not cause a reduction in the incidence of tumours, but it delayed their occurrence. The risk to develop various types of tumours during the third year of life was significantly higher in the ad libitum group than in the rats fed by a controlled regime. The automaton Han:CHRONOFEEDER, used in this study, has proved to be an appropriate, relatively inexpensive and easily installable feeding system for automatic control of food accessibility. It is suitable to implement controlled feeding and food restriction of rodents in longterm experiments.