Effect of n-3 and n-6 fatty acids on 7,12 dimethylbenz (a) anthracene-induced mammary tumorigenesis

Numerous studies have consistently shown that vegetable oils containing linoleic acid enhance mammary tumorigenesis more effectively than fish oils containing eicosapentaenoic and docohexaenoic acids. The purpose of this investigation was to study these and additional n-3 and n-6 PUFA, e.g., a-linolenic (a-LN) (18:3 n-3) and gamma-linolenic (GLA) (18:3 n-6) acid. Different oils were used as dietary sources of fatty acids: corn (CO) (61% LA); blackcurrant (BCO) (44% LA, 18% GLA and 16% a-LN); fish oil (FO) (mixed with corn oil, 12% LA and 24% EPA + DPA + DHA). Thirty-five-day-old female Sprague-Dawley rats were divided into 5 dietary treatment groups and were allowed to feed ab libitum on one of the test diets: I. BCO (23.5%); II. CO (23.5%); III. BCO (15.5%) + FO (8%); IV. FO (20.5%) + CO (3%); and V. BCO (20.5%) + FO (3%). From 48 to 52 days of age, rats in all five groups were fed rat chow. At 50 days of age, all rats were given 5 mg DMBA by oral intubation, and 2 days later the test diets were resumed until termination of the experiment. Analysis of tumor incidence, and multiplicity data for 5 diet groups indicated that rats fed 23.5% CO (II) exhibited enhanced mammary tumor yields when compared to animals on the remaining 4 diets in the order II greater than I, III, V greater than IV. Since the level of fat (23.5% w/w) was similar in all 5 diets, and body weight gain was in the order IV greater than II greater than I, the results of this study indicate that differences in tumor yields were related to fatty acid composition of diets. In support of this conclusion, fatty acid profiles of RBC and tumor phosphoglycerides reflected dietary fatty acid composition. In groups I and II, even though tumor levels of LA were similar, the levels of GLA, DHLA (20:3 n-6) and a-LN were higher in I compared to II, suggesting that these differences may be associated with lower yields of DMBA-induced mammary tumors in group I. Incorporation of marine type n-3 PUFA (EPA, DPA and DHA) in tumor PL was greater in Group IV compared to plant type n-3 PUFA (a-LN) in Groups I, III, and V. Since tumor yields were the lowest in Group IV, these results suggest that incorporation of marine type n-3 PUFA into cell membranes does not favor development of DMBA-induced mammary tumors.