INHIBITION OF ETHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE-INDUCED LUNGTUMORIGENESIS BY DIETARY OLIVE OIL AND SQUALENE

Epidemiological studies have suggested that frequent olive oil consump tion may be a protective factor against lung cancer formation. Squalen e, a characteristic compound in olive oil, is an inhibitor of 3-hydrox y-3-methylglutaryl coenzyme A reductase activity and has been proposed to inhibit the farnesylation of ras oncoproteins, The present study i nvestigated the effect of dietary olive oil and squalene in a mouse lu ng tumorigenesis model. Female A/J mice were fed AIN-76A diets contain ing 5% corn oil (control), 19.6% olive oil, or 2% squalene starting at 3 weeks before a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1 -butanone (NNK) (103 mg/kg, i.p.). Animals were maintained on their re spective diets throughout the study. At 16 weeks after NNK administrat ion, 100% of the mice in the control group had lung tumors with a tumo r multiplicity of 16 tumors per mouse. The olive oil and squalene diet s significantly (P < 0.05) decreased the lung tumor multiplicity by 46 and 58%, respectively. The squalene diet significantly (P < 0.05) dec reased lung hyperplasia by 70%, In mice fed a diet containing 2% squal ene for 3 weeks, the activation of NNK was increased by 1.4- and 2.0-f old in lung and liver microsomes, respectively, but its relationship t o the inhibition of carcinogenesis is not clear. These results demonst rate that dietary olive oil and squalene can effectively inhibit NNK-i nduced lung tumorigenesis.