DIFFERENTIAL-EFFECTS OF DIETARY LINOLEIC-ACID ON MOUSE SKIN-TUMOR PROMOTION AND MAMMARY CARCINOGENESIS

On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) wou ld also cause an enhancement in mouse skin-tumor promotion. SENCAR mic e were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation with 7,12-dimethylbenz(a)anthracen e and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol -13-acetate. An inverse correlation (r = -0.92) was observed between p apilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidenc e was also found. The fatty acid composition of epidermal phospholipid s reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetat e-induced epidermal prostaglandin E2 levels generally decreased with i ncreasing dietary LA. To determine whether this inverse correlation be tween dietary LA and tumor yield was due to species differences or org an-model differences, a mammary carcinogenesis experiment was performe d. SENCAR mice were fed the 0.8%, 4.5%, and 8.4% LA diets. All mice re ceived 6 mg 7,12-dimethylbenz(a)anthracene, administered intragastrica lly at 1 mg/week. Tumor appearance was delayed in the 0.8% LA diet gro up, and a positive dose-response relationship between dietary LA and m ammary-tumor incidence was observed. These studies suggest that the ef fect of dietary LA on tumor development is target tissue specific rath er than species specific.