Chemopreventive Efficacy of Kawain in UPII-mutant Ha-ras Mice

Cohorts of UPII-mutant Ha-ras mice were generated as described previously [6 (link),7 (link),8 (link)] and were provided (a) control diet (AIN93M diet) and (b) 0.6% kawain [0.6% kawain (w/w) in AIN-93M diet] (Dyets, Inc., Bethlehem, PA, USA) [8 (link)]. Each group contained 18 mice. These treatments started at four weeks of age and allow a one-week equilibration period after weaning. Comparable initial body weight was achieved in each group through a randomization process. Groups of survived mice were terminated at six months of age by CO₂ asphyxiation. We have recorded: (1) body weight and food consumption weekly, (2) time to death or sacrifice, (3) organ weight (heart, lung, liver prostate thymus, kidney, etc.) at the end of the experiment, (4) tumor burden (bladder and ureteral weight), (5) pathological changes: simple hyperplasia, nodular hyperplasia, and low-grade papillary carcinoma, and (6) obstructive uropathy [6 (link),7 (link),8 (link)]. The chemopreventive efficacies were comprehensively analyzed by comparing bladder and ureteral weight, survival time, pathological grade, incidence of hydronephrosis, and time to hematuria to the control groups. The approved protocol by UCI was followed (protocol #:2004-2540) for animal care and all experimental procedures.