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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #229386
Title: Fish oil supplementation inhibits NNK-induced lung carcinogenesis in the A/J mouse

Author
item MERNITZ, HEATHER - JM USDA HNRCA @ TUFTS
item LIAN, FUZHI - JM USDA HNRCA @ TUFTS
item Smith, Donald
item Meydani, Simin
item Wang, Xiang-Dong

Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2009
Publication Date: 10/13/2009
Citation: Mernitz, H., Lian, F., Smith, D., Meydani, S., Wang, X. 2009. Fish oil supplementation inhibits NNK-induced lung carcinogenesis in the A/J mouse. Nutrition and Cancer. 61(5):663-9.

Interpretive Summary: Consumption of fish oil containing high levels of omega-3 (n-3) polyunsaturated fatty acid (PUFA) ratio has been suggested to protect against many chronic diseases. However, its preventive role against cancer remains unresolved. Particularly, 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 month dietary supplementation with fish oil (with a n-6/n-3 ratio of 0.2) and corn oil (with an-6/n-3 ratio of 46.1), as compared with soybean oil (with the same n-6/n-3 ratio as the base diet, approximately 7.5), on lung tumor incidence and tumor number developed in a mouse model of chemical carcinogen-induced lung cancer. We found that dietary supplementation had no effect on overall lung tumor incidence but fish oil supplementation was able to decrease lung tumor number by 78% and 80%, compared to mice receiving soybean oil and corn oil supplementation, respectively. While no changes on the expression of many proteins that regulate cell growth, such as p27Kip1, cyclin D1 and cyclin E were observed, the inhibitory effect of fish oil on lung tumor number was associated with increased expression of a cell growth inhibitor protein p21Cip1 in the lungs. Furthermore, fish oil supplementation was shown to significantly increase the expression of enzymes that regulate fatty acid metabolisms, such as lipoxygenase isoforms 15-LOX and 12-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.

Technical Abstract: 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, its preventive role against cancer remains unresolved, and particularly, 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 month dietary supplementation with fish oil (with a n-6/n-3 ratio of 0.2) and corn oil (with an-6/n-3 ratio of 46.1), as compared with soybean oil (with the same n-6/n-3 ratio as the base diet, approximately 7.5), 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. While no changes on 27Kip1, cyclin D1 and cyclin E were observed, the inhibitory effect of fish oil on lung tumor prevalence was associated with increased expression of cell cycle inhibitor p21Cip1 in the lungs. Furthermore, fish oil supplementation was shown to significantly increase the expression of lipoxygenase isoforms 15-LOX and 12-LOX, but not 5-LOX, 8-LOX or cyclooxygenase-2 (COX-2) 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.