Fasting and postprandial triacylglycerol responses to a standard test meal in subjects taking dietary supplements of n-3 fatty acids.

diet is high 141. A number of mechanisms have been put forward to explain the effects of dietary fat o n mammary tumour incidence [ 1 I . Welsch & Aylsworth [51 have shown that dietary fat influences the mammographic response to exogenous hormones and have proposed that these effects may be mediated through dietary-fat-induced enhancement of the phosphoinositide signal transduction mechanism, secondary to altered mammary membrane phosphoinositide fatty acid composition [6]. The phosphoinositide fatty acid composition of the platelet membrane has been shown to be resistant to alterations in dietary fatty acid intake [ 7, 81. No studies have been undertaken to determine the susceptibility of mammary epithelial membrane phosphoinositide fatty acid composition to altered fatty acid intake. In the present study, tumour incidence and growth rates of carcinogen-treated animals, and the fatty acid compositions of mammary membrane choline (PC), ethanolamine (PE) and inositol (PI) phospholipids, of tissue from control and carcinogen-treated animals, have been studied in corn-oil, olive-oil and MaxEPA (fish-oil)-fed animals. Twenty-four, 30-day-old female Sprague-Dawley rats weighing approximately 80 g were treated with the carcinogen ENU (ethylnitrosourea; 5 mg of ENU administered by gastric gavage). Treated animals were randomly assigned to corn-oil, olive-oil or MaxEPA dietary groups. Twenty-four control (non-ENU-treated) animals were also randomly assigned to each of the three dietary groups. Food intakes and body weight were measured weekly and food pots changed daily. Animals in the ENU-treated group were killed when palpable mammary tumours could be felt at weekly examinations (between 16 and 20 weeks postcarcinogen). A control animal from the same dietary group was killed at the same time as the tumour-bearing animal. Tumours and normal mammary tissues were excised and weighed, lipids extracted and phospholipid classes separated by two-stage thin-layer chromatography [9]. PI, PC and PE fractions were analysed for their fatty acid compositions after methylation of hydrolysed phospholipids and se aration using packed-column gas-liquid chromatography r10 g of Silar I OC/100 g of Gas chrom. Q ( 100120 mesh)]. At 20 weeks after carcinogen administration, tumour incidence rates were significantly lower in MaxEPA (43"/0), compared with olive-oil (73%; P< 0.05), and corn-oil (63%; P< 0.05). -fed animals. In normal mammary tissue from control animals, differences in the fatty acid compositions of the PE and PC, but not the PI fractions, were found in animals fed MaxEPA. In PE, arachidonate (C20,4, ,,-,,) content was lower in MaxEPA (7.78 f I . 16, mean f s.E.M.), compared with corn-oil (13.27 f 1.54; I'< 0.01) and olive-oil ( 10.27 f 1.97; P < 0.05) -fed animals. Docosahexaenoic acid (C??:,, , -3) was higher in MaxEPA (4.39 k 0.66) than corn-oil (2.19f0.25; P<0.01) and olive-oil (2.63f0.35; 1'<0.05) -fed animals. Similar, but less marked, differences were found in the PC fraction of MaxEPA-fed animals, but no significant differences in phosphoinositide fatty acid composition were found between any of the three dietary groups. In tumour tissue no differences in the fatty acid composition o f any of the phospholipid classes were found in animals fed diets of different fatty acid composition. This study has confirmed the protective effects of ti 3 fatty acids against mammary tumour development in carcinogen-treated animals. Failure to detect differences in phosphoinositide fatty acid composition of normal mammary tissue obtained from animals fed diets of different fatty acid composition suggests that the composition of this membrane component is resistant to dietary fatty acid modification. The findings do not support the suggestion that dietary fatty acid-induced changes in phosphoinositide fatty acid composition underlie cnhanced mammogenic responses to exogenous hormones and enhanced tumour incidence rates observed in animals fed high fat diets.