The detection and measurement of lipid oxidation in biological systems and some biologic effects of this oxidation are reviewed. The role of lipid oxidation in the process of photocarcinogenesis and the protective effect of antioxidants against this process also are discussed. The mechanism of such protection is unknown and studies directed at elucidating the mechanism of antioxidant effect in photocarcinogenesis and in some other pathological conditions believed to involve, lipid oxidation are needed. In addition to this, epoxidation of lipids observed in monolayer studies requires further investigation, particularly in the presence of some other unsaturated molecules. The possible significance of such a study—particularly in the presence of polycyclic aromatic hydrocarbon carcinogens, where formation of epoxides is generally accepted as active intermediates-is also discussed. In addition, present knowledge on the role of lipid peroxides in the destruction of proteins and biomembranes, in chemically induced toxicity and in generation of singlet oxygen is presented.

Lipid oxidation: Biologic effects and antioxidants—A review

Publisher Summary Nutrition is related to the development of cancer in three ways: (1) food additives or contaminants may act as carcinogens, cocarcinogens, or both; (2) nutrient deficiencies may lead to biochemical alterations that promote neoplastic processes; and (3) changes in the intake of selected macronutrients may produce metabolic and biochemical abnormalities, either directly or indirectly, which increase the risk for cancer. Specific carcinogens play a minor role as initiators in the relationship between nutrition and the development of cancer. This chapter covers six types of cancer: large bowel cancer, colon carcinogenesis, stomach cancer, cancer of the upper alimentary and respiratory tract, cancer of the pancreas, and breast cancer. In four of these—breast, large bowel, stomach, and head and neck—the epidemiologic evidence is overwhelming that nutritional factors have a major etiological role. Dietary factors are also implicated in the etiologies of the two remaining types of cancer—pancreas and prostate—but the epidemiologic evidence is not overwhelming. The chapter also presents an evaluation of the status of the relationship between nutrition and cancer in man, discusses the use of animal models to determine if the etiological factors established for man can be modified in an experimental setting, and makes recommendations for additional research and possible preventive measures.

Nutrition and its relationship to cancer

Publisher Summary This chapter discusses fatty acids and immunity. Like all mammalian cells, lymphocytes contain a variety of fatty acids, some of which, the essential fatty acids, must be supplied to the cells because they are unable to synthesize them. Of the essential fatty acids, linoleic acid and the derivative arachidonic acid are major components of the phospholipids of lymphocyte membranes, while α-linolenic and its derivatives are only minor components. A wide variety of fatty acids produce effects on both the lymphoid and reticuloendothelial systems; the actual effects produced depend on the method of administration and the chemical nature of the fatty acid. Arachidonic acid is an immediate prostaglandin precursor and plays a central role in lymphocyte activation. Membrane phospholipid fatty-acid composition alters when lymphocytes are stimulated, either by antigen or by mitogens, such as phytohaemagglutinin or concanavalin A. Increased turnover of phospholipid fatty acids, following lymphocyte stimulation, requires a transferase to incorporate new fatty acids and a means of generating lysophosphatides and free fatty acids as substrates for this enzyme.

Fatty Acids and Immunity

The growth-promoting effect of dietary polyunsaturated fat is reported for six transplantable rat and mouse mammary adenocarcinomas which have different origins and characteristics. All six adenocarcinomas developed a significantly greater mass when implanted in animals receiving a 15% corn oil-containing diet than in animals receiving a fat-free diet. In the case of the two tumors implanted in BALB/c mice, addition of as little as 0.1% pure cis,cis-linoleic acid to a fat-free diet was as effective as 15% corn oil. However, in two tumors implanted in C3H mice, and in the rat tumor, 0.1% linoleic acid did not increase tumor weight. As little as 0.06% 5,8,11,14-eicosatetraynoic acid and 0.004% indomethacin, inhibitors of prostaglandin synthesis, in the diet prevented the tumor growth-promoting effect of polyunsaturated fat in BALB/c mice. The observed difference in tumor mass due to dietary fat could not be accounted for by differences in the duration of the latent growth period following tumor implantation. The neoplasms taken from animals fed either fat-free or corn oil-containing diets were analyzed for DNA, protein, total lipids, phospholipids, and cholesterol. There were no differences in the chemical composition which could account for the difference in tumor weight observed. The size of the proliferative cell population in tumors implanted in either BALB/c or C3H mice was not changed by dietary fat. Splenomegaly was observed in host BALB/c mice in direct proportion to the increase in tumor mass. Our results suggest that the growth-enhancing effect of dietary fat on transplantable mammary tumors (a) is caused by cis,cis-linoleate, (b) varies quantitatively with species and strain of animals, (c) cannot be accounted for by an increased neoplastic cell proliferation, and, therefore, (d) may be mediated through the cellular immune system with the possible involvement of prostaglandins in this process.

Effect of Dietary Polyunsaturated Fatty Acids on Growth of Mammary Adenocarcinomas in Mice and Rats

There are multiple lines of evidence that a variety of natural fatty acids are effective in health promotion. Among these fatty acids, conjugated linoleic acid (CLA)--a collective term referring to a mixture of positional and geometric isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic acid)--is currently under intensive investigation due to its health-promotion potential. The antitumor activity of CLA is of special interest, since it shows inhibitory effects against multistage carcinogenesis at relatively low dietary levels. Many studies using in vivo and in vitro models have shown that CLA suppresses the development of multistage carcinogenesis at different sites. The research to date on CLA has provided a vast amount of information about the mechanism on how CLA functions in the prevention of cancer. This article discusses characteristics of CLA in the prevention of cancer in both in vivo and in vitro studies and the possible underlying chemoprevention mechanisms.

Role of the conjugated linoleic acid in the prevention of cancer.

Female rats have been fed high fat diets containing either polyunsaturated or saturated fat. After being fed either of the diets for 4 weeks, some of the animals received an intragastric dose of 7,12-dimethylbenz(a)anthracene (DMBA). At this point, the diets of half of the animals were interchanged so that animals previously fed the polyunsaturated fat diet were fed the saturated fat diet and vice versa. The cumulative incidence of tumor-bearing rats among DMBA-dosed rats was greater when the polyunsaturated fat diet was fed. The mean induction time of tumors decreased and the proportion of tumor-bearing rats which developed malignant tumors increased when the polyunsaturated fat diet was fed. This promotional effect of the polyunsaturated fat diet was exerted only when the diet was fed after DMBA administration.

Effect of dietary fats on the incidence of 7,12‐dimethylbenz(a)‐anthracene‐induced tumors in rats

The effect of a diet containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in C3H-A vyfB mice was examined. After receiving either diet for 28 days, some of the mice were given an intragastric dose of 5 mg DMBA. To identify the stage of carcinogenesis that might be influenced by dietary fat, the diets of half of the mice were then interchanged so that those previously fed the saturated fat diet were fed the polyunsaturated fat diet and vice versa. The cumulative incidence of tumor-bearing mice was significantly greater among the females fed the polyunsaturated fat diet compared to those fed the saturated fat diet. This enhancement of carcinogenesis was observed only when the mice were fed the polyunsaturated fat diet after DMBA administration. Similar trends were observed in the male mice, but these mice developed fewer tumors and none of the differences between the tumor incidences were statistically significant. The most common sites for tumors in the male mice were the liver, lungs, and skin, whereas those for tumors in the females were the mammary glands and ovaries. The differences in tumor incidence suggest that carcinogenesis was enhanced by the polyunsaturated fat diet during the promotion stage of carcinogenesis.

G. J. Hopkins

Papers

Effect of dietary fats on the incidence of 7,12‐dimethylbenz(a)‐anthracene‐induced tumors in rats

Carcinogenesis Induced by 7,12-Dimethylbenz[a]anthracene in C3H-A vyfB Mice: Influence of Different Dietary Fats