Fish Oil Supplementation Inhibits NNK-Induced Lung Carcinogenesis in the A/J Mouse

High intake of fish oil with a low omega-6 (n-6)/omega-3 (n-3) polyunsaturated fatty acid (PUFA) ratio has been suggested to protect against many chronic diseases. However, the effect of different ratios of dietary n-6 and n-3 PUFA on lung tumorigenesis has not been investigated. In this study, we examined the effect of a 4 mo dietary supplementation with corn oil (with a high n-6/n-3 ratio) and fish oil (with a low n-6/n-3 ratio) as compared with soybean oil (isocaloric control with the same n-6/n-3 ratio as the base diet) on tumor incidence and tumor prevalence in the A/J mouse model of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis. We found that dietary supplementation had no effect on overall lung tumor incidence, but fish oil supplementation was able to decrease lung tumor prevalence by 78% and 80% compared to groups receiving soybean oil and corn oil supplementation, respectively. The inhibitory effect of fish oil on lung tumor prevalence was associated with increased expressions of cell cycle inhibitor p21Cip1 and lipoxygenase isoform 15-LOX in the lungs. These data suggest that fish oil with a low ratio of n-6/n-3 PUFA could be beneficial in the prevention of lung carcinogenesis.