VARYING EFFECT OF DIETARY LIPIDS AND AZOXYMETHANE ON EARLY STAGES OF COLON CARCINOGENESIS - ENUMERATION OF ABERRANT CRYPT FOCI AND PROLIFERATIVE INDEXES

Animal models have been used extensively to study the role of diet in the etiology and prevention of colon cancer. It is recognized that sev eral experimental variables affect disease modulation and outcome. Our objective was to determine whether an interaction between the dose of carcinogen used and dietary factors exist, using aberrant crypt foci (ACF) as a biological end point. Sprague-Dawley male rats were injecte d with a low or a high dose of azoxymethane (AOM, 5 mg or 20 mg per kg s.c.) or saline (0.2 ml/animal s.c.), and randomly allocated to four diet groups (N = 8/group) 1 week later. Diets varied with respect to t ype of fat (corn or olive oil) and levels of fat: normal(5 g/100 g) co rn or olive oil (CO or OO), or high (23.5 g/100 g) corn or olive oil ( HCO or HOG). After 8 weeks of dietary treatment animals were injected with colchicine (1 mg/kg). Two and a half hours later they were killed and their colons assessed for number of ACF, number of crypt/focus (c rypt multiplicity), and the size of ACF as well as the number of cells in metaphase and their location in the crypt section. The low dose of AOM induced fewer ACF and ACF with higher crypt multiplicity than did the high dose of AOM. Dietary fats exerted a variable effect on ACF, depending on the dose of AOM. In low-dose AOM groups, both CO diets ex erted a growth-enhancing effect on ACF compared with OO diets. In the higher dose AOM groups, the HCO group had more (p less than or equal t o 0.05) ACF with greater than or equal to 3 crypts per focus than did the CO group (18.2 vs. 10.7). The OO groups were similar to the HCO gr oup. The dose of AOM used was an important variable and had a signific ant effect on the total number of ACF, the number of ACF with greater than or equal to 3 crypts per focus, the average size of ACF, and the size of crypts per focus. There was a significant interaction between the type and level of fat and of AOM dose in modifying the number of A CF with greater than or equal to 3 crypts per ACF, the mean AC/ACF, an d the size of ACF. The level of fat was an important variable in affec ting the number of mitotic cells. Animals fed a high-fat diet had lowe r mitotic activity than those fed normal fat diets. The ability of a d iet to modulate early events during colon carcinogenesis depended on t he doses of carcinogen employed.