INHIBITION OF RAT MAMMARY TUMORIGENESIS BY DIETARY-CHOLESTEROL

The effects of dietary cholesterol and oxidized cholesterol on mammary tumor development were examined in female Sprague-Dawley rats exposed to the carcinogen N-methyl-N-nitrosourea (MNU), Animals were administ ered 50 mg/kg MNU at 50 days of age and fed either a control (AIN-76) diet or the control diet supplemented with 0.3% cholesterol or 0.3% ox idized cholesterol for up to 26 weeks. The oxidized cholesterol was pr epared by heating cholesterol at 110 degrees C for 48 h, Gas chromatog raphic analysis of the oxidized cholesterol revealed a 2% yield of oxi dation products in addition to a large amount of unchanged cholesterol (>96%), Tumor incidence in the cholesterol group (67%) was significan tly lower than in the control group (96%, P < 0.05), but the oxidized cholesterol group (79%) was not significantly different from the contr ol or cholesterol groups, Average number of tumors per animal was lowe r in the cholesterol group (1.5) than in the control (2.8) or oxidized cholesterol groups (2.3, P < 0.005), Serum low density lipoprotein (L DL) cholesterol was greater in the cholesterol (185 +/- 38 mg/dl) and the oxidized cholesterol groups (160 +/- 34 mg/dl) than in the control s (55 +/- 4 mg/dl, P < 0.05), although there was no difference between the cholesterol and the oxidized cholesterol groups, These results sh ow that dietary cholesterol inhibits mammary tumor development in this model, Elevated serum LDL cholesterol may inhibit de novo cholesterol synthesis in preneoplastic and/or tumor cells, thereby inhibiting the ir proliferation.