CHEMOPREVENTIVE EFFICACY OF LOW-DOSE OF PRAVASTATIN, AN HMG-COA REDUCTASE INHIBITOR, ON 1,2-DIMETHYLHYDRAZINE-INDUCED COLON CARCINOGENESIS IN ICR MICE

Potential chemopreventive action of de-escalated doses of pravastatin (Pr), an HMG-CoA reductase inhibitor, on 1,2-dimethylhydrazine . 2HCl (DIMH)-induced colon tumorigenesis was evaluated in ICR mice. Thirty m ice each in 4 groups received an intraperitoneal injection of 20 mg DM H/kg body weight once meekly for 10 weeks, and were given drinking wat er dissolved Pr at the concentration of 10 ppm, 5 ppm, 1 ppm or 0 ppm (control) throughout the experiment. The incidence of colon tumors exa mined at week 35 was significantly lower in the Pr-treated groups than the control group: 20%, 21% and 23% vs. 55%. However, the tumor multi plicity/tumor-bearing animal was increased in the Pr-treated groups co mpared to the control group. Of all the tumors, 66 were adenocarcinoma s in the distal colon and 5 mere squamous cell carcinomas at the anus. The Pr treatment showed no hypocholesterolemic effect but did signifi cant decrease of colonic mucosal cholesterol. The results seems to sug gest that a small dose of Pr may reduce the incidence of colon cancers , perhaps being related, at least in part, to modulation of cholestero l synthesis in situ at the colonic mucosa.