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) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice 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)anthracene and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol-13-acetate. An inverse correlation (r = -0.92) was observed between papilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidence was also found. The fatty acid composition of epidermal phospholipids reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetate-induced epidermal prostaglandin E2 levels generally decreased with increasing dietary LA. To determine whether this inverse correlation between dietary LA and tumor yield was due to species differences or organ-model differences, a mammary carcinogenesis experiment was performed. SENCAR mice were fed the 0.8%, 4.5%, and 8.4% LA diets. All mice received 6 mg 7,12-dimethylbenz(a)anthracene, administered intragastrically at 1 mg/week. Tumor appearance was delayed in the 0.8% LA diet group, and a positive dose-response relationship between dietary LA and mammary-tumor incidence was observed. These studies suggest that the effect of dietary LA on tumor development is target tissue specific rather than species specific.
Fischer
S M
SM
University of Texas M.D. Anderson Cancer Center, Research Division, Smithville 78957.
Leyton
J
J
Lee
M L
ML
Locniskar
M
M
Belury
M A
MA
Maldve
R E
RE
Slaga
T J
TJ
Bechtel
D H
DH
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D015232:Dinoprostone / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis / Q000737:chemistry; D005260:Female; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051379:Mice; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate
D004041:Dietary Fats; D005227:Fatty Acids; D008041:Linoleic Acids; D015127:9,10-Dimethyl-1,2-benzanthracene; D019787:Linoleic Acid; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate