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-dimethylhydrazin e (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 drinkin g 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 a t weeks 25 or 30. Histologically most of the tumors were well-differen tiated adenocarcinomas. The incidence of colon tumors examined at week s 25 or 30 was reduced by 67% in the 0.01% Pr group, by 30% in the 0.0 05% 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 differen ces did not reach statistical significance. The number of tumors per m ouse was significantly reduced in all groups administered Pr and Si ex cept 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 labor atory animal model.