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 (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.
Narisawa
T
T
Akita University College of Allied Medical Science, Japan.
Fukaura
Y
Y
Tanida
N
N
Hasebe
M
M
Ito
M
M
Aizawa
R
R
D019813:1,2-Dimethylhydrazine; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004127:Dimethylhydrazines; D004305:Dose-Response Relationship, Drug; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014881:Water Supply
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019813:1,2-Dimethylhydrazine; D017035:Pravastatin