MODULATION OF ABERRANT CRYPT FOCI BY DIETARY-FAT AND CALORIC RESTRICTION - THE EFFECTS OF DELAYED INTERVENTION

Recent investigations have established that caloric restriction (CR) r educes end tumor incidence in the rat colon. The present study was con ducted to determine whether CR at the level of 20% of the ad libitum ( AL) intake and dietary fat would alter the growth of intermediate pren eoplastic colonic aberrant crypt foci (ACF). F344 rats were given inje ctions of 15mg/kg azoxymethane, fed AL for 11 weeks, and then allocate d to 1 of 4 dietary groups (n - 20/group): high fat (23% w/w) or low f at (5% w/w) AL (HFAL, LFAL), or high fat or low fat CR (HFCR, LFCR). A fter 4 weeks only the HFAL and HFCR groups had identifiable adenomas w ith incidences of 50 and 30%, respectively. There was a significant po sitive correlation between total fat consumed/day (grams) and the numb er of ACF with 4-6 crypts focus. After 12 weeks of feeding, the total number of ACF was lower (P less-than-or-equal-to 0.05) in the CR group s relative to the AL groups in both the high and low fat diets. The nu mber of ACF with 4-6 crypts/focus and >6 crypts/focus were lower in th e LFCR group compared to the LFAL group, whereas the number of ACF wit h 1-3 crypts/focus was lower in the HFCR group compared to the HFAL gr oup. CR was the main variable affecting the number and growth of ACF a t week 12. Positive correlations were demonstrated between increased m ean daily intake of energy and the number of total ACF/colon, ACF with 4-6 crypts/focus, and ACF with >7 crypts/focus at week 12. Cell proli feration indices did not correlate with ACF or tumor incidence data. T hese findings demonstrated that (a) dietary fat affects tissue growth characteristics more rapidly than CR, (b) CR alters the development of ACF depending on the level of fat and experimental duration, and (c) ACF with varying growth features respond differently to CR and dietary fat. These findings also suggest that subtle dietary manipulations in fat and caloric content used at the later stages of colon carcinogene sis can modulate tumor development.