Inability of low- or high-fat diet to modulate late stages of colon carcinogenesis in Sprague-Dawley rats.

The main objective of the present proposal was to investigate the effect of feeding a low- or high-fat diet in the early and late stages of colon carcinogenesis. Sprague-Dawley male rats were injected with azoxymethane (20 mg/kg/week) for 2 weeks. One week later they were randomly allocated to eat a low-fat (4% beef tallow + 1% corn oil) or a high-fat (18.6% beef tallow + 4.7% corn oil) diet (LF or HF). After 10 weeks of feeding, 10 animals per group were killed, and their colons were evaluated for tumors. The remaining animals in each group were divided further into LF and HF groups. The four experimental groups consisted of groups receiving LF or HF diet throughout the study (LF-LF or HF-HF) and the groups fed LF or HF diet for the first 10 weeks, then assigned the alternate diet for the remainder of the duration (LF-HF or HF-LF). By week 26, the remaining animals were killed, and their colons were evaluated for the number, location and size of tumors. The tumor incidence in the HF-HF and HF-LF groups were higher than the LF-LF and LF-HF groups (81.6 and 84.8% versus 71.4 and 60.0%). Tumor multiplicity ranged from 1.86 +/- 0.26 to 2.54 +/- 0.33 in all groups. The average size of tumors and total tumor area/rat were affected significantly by the time at which the diet was fed. Average size and total tumor area in the animals fed HF diet during early stages (HF-HF and HF-LF) were significantly higher than those fed the LF diet during the early stages. Late intervention by specific diets did not affect tumor outcome. Sequential enumeration of aberrant crypt foci of different growth features representing early preneoplastic stages corroborated the findings of the tumor outcome. It was concluded that early preneoplastic stages were more sensitive than their advanced counterparts to the dietary interventions of the present study.