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Selenised casein protects against AOM-induced colon tumors in Sprague Dawley rats.Selenium (Se) has been shown to be protective against cancers in animal models at concentrations exceeding those considered essential for normal nutritional requirements. Organic forms of Se provided as dairy proteins were obtained from cows fed diets supplemented with yeast Se. The casein extracted from milk was found to contain approximately half the Se of the Se-enriched milk. This casein was included in a semi-purified AIN rodent diet so as to provide 1 ppm Se and 25% protein and was compared with AIN diets containing no added Se (control, 0.05 ppm), 1 ppm and 4 ppm Se as selenised yeast (Sel-Plex) Their influence on colon tumor expression was examined in rats induced with azoxymethane, the diets being introduced post-induction. The selenised casein diet at this concentration was effective in reducing colon tumor incidence (by 29%) and burden (decreased 52%, P < 0.05) relative to the control in rats 26 wk post-induction. Selenised yeast, when added at similar (1 ppm) and increased Se concentration (4 ppm), did not influence significantly colon tumor expression. However, in a second study, with Se yeast providing Se at 1 ppm, 4 ppm, and 8 ppm throughout the experiment, a significant reduction in tumors was observed with 8 ppm Se (colon tumor incidence was 15% lower and colon tumor burden was 35% lower, P < 0.05). However this was associated with a significantly lower body weight in the rats (down 10.5%, P < 0.05) indicating a possible disturbance with normal energy intake or metabolism. The form in which Se is presented in the diet may influence significantly its bioavailability and/or anticancer potential at given concentrations within a safe range. The efficacy of selenised casein and indeed other potential dietary sources deserve further investigation with regard to their ability to prevent colon tumors at concentrations considered safe in the diet.