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Potential chemopreventive action of de-escalated doses of pravastatin (Pr), an HMG-CoA reductase inhibitor, on 1,2-dimethylhydrazine.2HCl (DMH)-induced colon tumorigenesis was evaluated in ICR mice. Thirty mice each in 4 groups received an intraperitoneal injection of 20 mg DMH/kg body weight once weekly for 10 weeks, and were given drinking water dissolved Pr at the concentration of 10 ppm, 5 ppm, or 0 ppm (control) throughout the experiment. The incidence of colon tumors examined at week 35 was significantly lower in the Pr-treated groups than the control group: 20%. 21% and 23% vs. 55%. However, the tumor multiplicity/tumor-bearing animal was increased in the Pr-treated groups compared to the control group. Of all the tumors, 66 were adenocarcinomas in the distal colon and 5 were squamous cell carcinomas at the anus. The Pr treatment showed no hypocholesterolemic effect but did significant decrease of colonic mucosal cholesterol. The results seems to suggest that a small dose of Pr may reduce the incidence of colon cancers, perhaps being related, at least in part, to modulation of cholesterol synthesis in situ at the colonic mucosa.

tohoku journal of experimental medicine

Chemopreventive Efficacy of Low Dose of Pravastatin, an HMG-CoA Reductase Inhibitor, on 1, 2-Dimethylhydrazine-Induced Potential chemopreventive action of de-escalated doses of pravastatin (Pr), an HMG-CoA reductase inhibitor, on 1,2-dimethylhydrazine . 2HCl (DMH)-induced colon tumorigenesis was evaluated in ICR mice.