Atorvastatin and suberoylanilide hydroxamic acid (SAHA) were evaluated for 
chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced 
by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 
mg/kg atorvastatin, and combinations containing SAHA and atorvastatin 
administered in their diet. SAHA and both combinations, but not atorvastatin, 
decreased the multiplicity of lung tumors, including large adenomas and 
adenocarcinomas with the combinations demonstrating the greatest efficacy. In 
Experiment 2, lung tumors were induced by 
4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol in strain A/J mice followed by 
180 mg/kg atorvastatin, 500 mg/kg SAHA, or both drugs administered in the diet. 
SAHA and the combination of both drugs, but not atorvastatin alone, decreased 
the multiplicity of lung tumors and large tumors, with the combination 
demonstrating greater efficacy. In Experiment 3, lung tumors were induced by 
1,2-dimethylhydrazine in Swiss-Webster mice followed by 160 mg/kg atorvastatin, 
400 mg/kg SAHA, or a combination of both drugs administered in the diet. SAHA 
and the combination, but not atorvastatin, decreased the multiplicity of lung 
tumors with the combination demonstrating greater efficacy. The multiplicity of 
colon tumors was decreased by SAHA, atorvastatin, and the combination, without 
any significant difference in their efficacy. mRNA expression analysis of lung 
tumor bearing mice suggested that the enhanced chemopreventive activity of the 
combination is related to atorvastatin modulation of DNA repair, SAHA modulation 
of angiogenesis, and both drugs modulating invasion and metastasis pathways. 
Atorvastatin demonstrated chemoprevention activity as indicated by the 
enhancement of the efficacy of SAHA to prevent mouse lung tumors.