Dose-response effects of the XXXX inhibitor, @entity12698 , on the chemoprevention of mammary carcinogenesis.

@entity3653 @entity12698 @entity0 @entity5 @entity106 @entity35 @entity4665
Recent chemopreventive studies in our laboratories showed that the @entity4665 inhibitor, @entity12698 , inhibited the induction of mammary @entity5 by @entity3653 ( @entity106 ). In this study, we examined the relative chemopreventive effect of varying doses of @entity12698 on the development and growth of @entity106 -induced @entity35 mammary @entity5 . At 10 days prior to receiving a single intragastric dose of 15 mg @entity106 / @entity35 , female @entity35 were fed a control chow diet or diets containing 250, 500, 1000 or 1500 ppm @entity12698 until termination of the experiment. Administration of increasing doses of @entity12698 inhibited mammary @entity5 incidence and multiplicity as well as @entity5 volume in a dose-dependent manner. At 122 days post @entity106 -intubation, mammary @entity5 incidence was 100% in the control @entity35 compared to 80%, 50%, 45% and 25% in @entity35 receiving 250, 500, 1000 or 1500 ppm @entity12698 , respectively (p<0.001). Similarly, @entity5 multiplicity and @entity5 volume were significantly reduced by increasing the dose of @entity12698 from 250 to 1500 ppm in the diet. The control @entity35 had an average of 3.46 @entity5 / @entity35 compared to 1.80, 1.00, 0.75 and 0.50 @entity5 / @entity35 in animals receiving 250, 500, 1000 or 1500 ppm @entity12698 , respectively (p<0.001). Average @entity5 volumes in @entity35 fed 250, 500, 1000 or 1500 ppm @entity12698 were 0.42, 0.34, 0.31 and 0.16 cm3 compared to 1.29 cm3 in the control @entity35 (p<0.001). There was a concomitant increase in the steady-state serum concentration of @entity12698 with the dose. These results indicate that, in this @entity35 model, the chemopreventive effect of @entity12698 against @entity0 is dose-dependent and that @entity12698 is effective even at lower dose levels.
