Morphological and cell kinetic effects of dietary manipulation during colorectal carcinogenesis.

The effect of dietary manipulation of fat and fibre on the structural and cell kinetic characteristics of colonic mucosa was studied before and during experimental carcinogenesis in 232 male Albino Swiss rats. Carcinogen treated animals were given 12 weekly injections of azoxymethane (10 mg/kg/week). The animals were divided between four dietary groups (1) high fat, high fibre, (2) low fat, high fibre, (3) high fat, low fibre and (4) low fat, low fibre. Pathological and cell kinetic information together with details of certain faecal characteristics was collected when the animals were killed 4, 20, and 28 weeks after starting their experimental diet. Tumour induction was significantly influenced by diet. The highest risk of colorectal tumour development was found in groups fed diet 3: high fat, low fibre (p less than 0.03). In contrast, diet 2: low fat, high fibre was associated with the lowest risk. The proportion of histologically proven colonic tumours occurring in each dietary group was: diet 1-10.9%, diet 2-3.6%, diet 3-63.7%, diet 4-21.8%. Scanning electron microscopic (SEM) studies done on selected samples indicated both dietary and azoxymethane related alterations in crypt unit integrity. The most marked surface architectural changes were seen in carcinogen treated animals maintained on diet 3 (high fat, low fibre). Stathmokinetic analysis revealed considerable intergroup variability. Both fat and fibre produced significant effects, principally during the preneoplastic phase of carcinogenesis. Faster proliferative activity tended to be found in animals at low risk of tumour induction (diet 2), slower proliferation being more characteristic of animals at high risk (p less than 0.05). The findings suggest that both topographical and cell kinetic parameters have an important relationship with promoting and protecting dietary factors during the development of colorectal cancer.