Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis by dietary olive oil and squalene

Epidemiological studies have suggested that frequent olive oil consumptionmay be a protective factor against lung cancer formation. Squalene, acharacteristic compound in olive oil, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and has beenproposed to inhibit the farnesylation of ras oncoproteins. The presentstudy investigated the effect of dietary olive oil and squalene in a mouselung tumorigenesis model. Female A/J mice were fed AIN-76A diets containing5% corn oil (control), 19.6% olive oil, or 2% squalene starting at 3 weeksbefore a single dose of 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone(NNK) (103 mg/kg, i.p.). Animals were maintained on their respective dietsthroughout the study. At 16 weeks after NNK administration, 100% of themice in the control group had lung tumors with a tumor multiplicity of 16tumors per mouse. The olive oil and squalene diets significantly (P <0.05) decreased the lung tumor multiplicity by 46 and 58%, respectively.The squalene diet significantly (P < 0.05) decreased lung hyperplasia by70%. In mice fed a diet containing 2% squalene for 3 weeks, the activationof NNK was increased by 1.4- and 2.0-fold in lung and liver microsomes,respectively, but its relationship to the inhibition of carcinogenesis isnot clear. These results demonstrate that dietary olive oil and squalenecan effectively inhibit NNK-induced lung tumorigenesis.