Effect of dietary oxidized cholesterol on azoxymethane-induced colonic preneoplasia in mice

The effect of cholesterol and oxidized cholesterol on azoxymethane-induced colonic preneoplasia was evaluated in C57BL/6J and BALB/cJ mouse strains. Mice were fed either a control AIN 76 semisynthetic diet or the control diet supplemented with 0.1% or 0.3% cholesterol, or 0.1% or 0.3% oxidized cholesterol for an 8-week period. For the first 4 weeks of the experiment, mice received weekly injections of azoxymethane (5 mg/kg body weight). Dietary cholesterol increased fecal concentrations of neutral and acid sterols. A dose-response relationship was observed in both mouse strains between the level of dietary cholesterol or oxidized cholesterol and formation of preneoplastic aberrant crypt foci. Enhanced cell proliferation along with alterations in several crypt morphometric parameters were also observed. These anomalies were enhanced to a greater extent by oxidized cholesterol. This data shows a very strong effect of cholesterol in enhancing the development of preneoplastic lesions in chemically induced cells. It also demonstrated that the state of oxidation of cholesterol influences colonic preneoplasia. This factor has been overlooked in previous animal experiments.