A new dietary model to study colorectal carcinogenesis: Experimental design, food preparation, and experimental findings

Abstract

Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients

“…6 -20 These and subsequent studies used measurements of large bowel epithelial proliferation or adenomatous polyp recurrence rates as intermediate biomarkers to evaluate the response to calcium supplements, or to different levels of dietary calcium intake, or even to feeding a human-like diet to animal models. [21][22][23][24][25][26][27][28][29][30] However, results of a number of international ecological and analytic epidemiologic studies did not support the hypothesis that calcium-deficient diet is a risk for colorectal cancer and did not find a cancer preventive value for calcium supplementation in humans. 11,13,14,16,22,26,31,32 These findings were in contrast to the findings of experimental studies in animals, where a calcium deficient or supplemented diet had a marked protective effect on large bowel epithelial proliferation and also on the process of carcinogenisis.…”

Effect of low or high glycemic load diets on experimentally induced mammary carcinogenesis in rats

“…Feeding human diets to rodents has precedent, although the approach has been infrequently used in investigations of diet, nutrition and cancer . The preparation of human diets in a manner that could be fed to rodents provided the same glycemic response in the rat as was predicted by calculation based on glycemic index and glycemic load data determined in human participants (Fig.…”

Diet and Cancer Prevention Research: From Mechanism to Implementation

“…Some studies have focused on combinatorial effects of nutrients on tumorigenesis, including testing factorially the interactions of several compounds [8]. In contrast, only a few studies of diet and cancer have fed human diets or diets with the equivalent level of complexity, to rodents [9][10][11]. Identifying approaches to conducting interventions in animals that more closely align with the complexity of dietary patterns in humans is important for moving forward the field [12].…”