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Previous studies suggested that a whey protein hydrolysate diet could inhibit chemical carcinogen-induced tumor incidence. Aberrant crypt foci are routinely used as intermediate end-point biomarkers of colon neoplasia; however, their suitability in response to dietary factors is equivocal. This study examined: a) lifetime ingestion of WPH in the prevention of AOM-induced tumors in small and large intestine; and, b) the association between ACF formation and later tumor incidence. Pregnant Sprague-Dawley rats were fed AIN-93G diets containing casein (20%, CAS as control) or WPH (20%) as the sole protein source starting on gestation day 4. Male progeny were weaned to the same diet as their dam and this diet was continued until termination of the experiment. Rats received AOM (15mg/kg body weight; s.c.) or an equal volume of saline at days 50 and 57 postnatal. At 6, 12, 20, and 23 weeks after AOM treatment, ACF and tumors were evaluated. Lifetime ingestion of WPH affected the temporal appearance of ACF. Six weeks after AOM, WPH-fed rats had significantly less total ACFs (P = 0.03) and ACFs containing 2 crypts (P = 0.01), 3 crypts (P = 0.019), and 4 or more crypts (P = 0.017) relative to CAS-fed rats; similar effects of WPH on ACF were observed at 23 weeks post-AOM. However, no effects of diet on ACF were found at 12 or 20 weeks after AOM administration. ACF multiplicity (number of crypts/ACF) was not affected by diet. WPH affected AOM-induced tumor incidence and progression. At 20 weeks post-AOM, WPH-fed rats had decreased incidence of small plus large intestine tumors compared to CAS-fed rats (P = 0.06, 20% vs. 60%); whereas, colonic tumor incidences were 13.3% vs. 40%, and small intestinal tumor incidences were 6.7% vs. 26.7% in WPH or CAS rats, respectively. At 23 weeks after AOM, differences in colon tumor incidence were not observed; however, WPH rats had fewer numbers of small intestinal tumors than did CAS rats (P = 0.004, 7.6% vs. 26%). Additionally, incidence of intestinal adenomas was decreased by WPH at 23 weeks post-AOM (P = 0.023, 7.6% vs. 21.9%); WPH-fed rats exhibited a trend (P = 0.09) for reduced small and large intestine tumor multiplicity. No ACF or tumors were observed in saline-treated rats. In summary, lifetime ingestion of WPH inhibited AOM-induced intestinal tumorigenesis. There was general agreement between relative ACF and tumor incidence only at early and late stages of tumorigenesis. Data suggest that arbitrarily timed ACF counts may not always predict the preventive effects of dietary factors on intestinal tumorigenesis. (USDA CRIS 6251-5100-002-06S).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]