Prevention of 1,2-dimethylhydrazine-induced colon tumorigenesis by HMG-CoA reductase inhibitors, pravastatin and simvastatin, in ICR mice.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin (Pr) and simvastatin (Si), suppressed 1,2-dimethylhydrazine (DMH)-induced colon cancer development in female ICR mice. All mice received an i.p. injection of 10 mg DMH/kg body wt once weekly for 15 weeks. Pr was administered at 0.01, 0.005 and 0.001% levels in drinking water, and Si at 0.01 and 0.002% levels in the diet. All animals had access to Pr or Si throughout the experiments which were terminated at weeks 25 or 30. Histologically most of the tumors were well-differentiated adenocarcinomas. The incidence of colon tumors examined at weeks 25 or 30 was reduced by 67% in the 0.01% Pr group, by 30% in the 0.005% Pr and 0.01% Si groups, and by 24% in the 0.001% Pr and 0.002% Si groups, compared with their respective controls. However, the differences did not reach statistical significance. The number of tumors per mouse was significantly reduced in all groups administered Pr and Si except the 0.001% Pr group as compared to their respective controls. The results from those three independent experiments seem to suggest that HMG-CoA reductase inhibitors may prevent colon tumorigenesis in laboratory animal model.
Narisawa
T
T
Akita University of Allied Medical Science, Japan.
Fukaura
Y
Y
Terada
K
K
Umezawa
A
A
Tanida
N
N
Yazawa
K
K
Ishikawa
C
C
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D002784:Cholesterol / Q000097:blood; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D004127:Dimethylhydrazines; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D017035:Pravastatin / Q000627:therapeutic use*; D019821:Simvastatin
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D019813:1,2-Dimethylhydrazine; D017035:Pravastatin