Influence of a dietary fiber on development of dimethylhydrazine‐induced aberrant crypt foci and colon tumor incidence in wistar rats

Abstract

Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 weeks were used as initiator. The rats were fed different levels of the fiber in a preinitiation period, during initiation, or in a postinitiation period. In general, the results showed a statistically significant inverse relation between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small ACF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process. The lack of correlation between the outcome of ACF and tumors could be related to the observation that statistically significant differences between groups were seen only in the total number of ACF and number of small ACF. The hypothesis that ACF are preneoplastic lesions needs to be supported by further experimental data. The present state of knowledge could indicate that ACF represent true preneoplastic lesions progressing into colon tumors or that ACF and colon tumors represent two parallel independent events as a consequence of the cancer initiation (i.e., the ACF not being preneoplastic lesions per se).

Development and Distribution of 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]‐pyridine (PhIP)‐induced Aberrant Crypt Foci in the Rat Large Intestine

“…The biological fate of other ACF, which tend to be localized proximally and to develop later, might be of greater significance for neoplasia. Several authors 15,25) have reported poor correlations between the incidence of cancer and the number and size of ACF, but this could be partly explained by heterogeneity of ACF, as shown here, whatever the case. Considering the distribution of large bowel tumors in human patients, PhIP could be a candidate carcinogen responsible to some extent for the recent increase of proximal colon cancers.…”

Distribution of lymphoid nodules, aberrant crypt foci and tumours in the colon of carcinogen-treated rats

“…But because neither the number nor the size of ACF has proved a significant predictor of AC formation along the length of the colon in the rat model system (this report) or in the mouse (Carter et al, 1994), the use of the total numbers or size of ACF in the colon of rats is not necessarily a valid indicator of the risk of malignant colon cancer. Indeed, there are now several reports from independent studies which fail to confirm numbers of ACF as a reliable indicator of cancer risk throughout the colon of rats (Hardman et al, 1991;Caderni et al, 1995;Thorup et al, 1994).…”

“…It also seems that there is no direct proof that any aberrant crypt foci progress to become malignant cancer, nor is there direct proof to the contrary. The question remains: do ACF represent true premalignant lesions which on rare occasion progress via a multistep process to become ACs or do ACF and colon AC represent end points of two parallel but independent pathways resulting as a consequence of a common colon cancer initiation (Thorup et al, 1994;Jen et al, 1994;Smith et al, 1994;Yamashita et al, 1995;Pretlow, 1995)? Serial observations using endoscopic procedures on humans and on animal models followed by terminal histology may eventually provide direct evidence on the fate of ACE.…”

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

“…At light microscopy the ACF are larger and have a thicker epithelial lining than normal crypts (6). The ACF assays have been used for the detection of factors that influence the modifiers of early colorectal carcinogenesis in rats treated with the chemical carcinogen DMH (7).…”