William J. Mergens

α-Tocopherol (Vitamin E) and Its Relationship to Tumor Induction and Development

In recent years, emphasis on the role of the chemical and biological environment in carcinogenesis has emerged. Some have suggested that the majority of all human cancers may be environmentally related (Higginson, 1976). Such developments have, in part, their origins in the recognition that geographical differences in cancer patterns exist in the world, and they are certainly related to variations in environment (Clemmesen, 1965; Doll et al., 1970; Segi et al., 1969). In general, it has also been observed that as migrant groups leave their previous environment and adopt a new one, their propensity toward specific cancers also shifts to the prevailing risk of the new country or even local area. Further weight has been added to this idea through the identification in the human environment of numerous carcinogenic substances such as polynuclear aromatic hydrocarbons, nitrosamines, nitrosamides, and aflatoxins. The presence of many of these entities in our environment and food supplies or from in vivo formation leaves little doubt about potential exposure to man.

EFFICACY OF VITAMIN E TO PREVENT NITROSAMINE FORMATION

In the early 1920s. vitamin E was described as a substance important for reproduction in rats,’ and since then, many studies have detailed the beneficial effects of vitamin E which basically entail its role in the maintenance of the reproductive, central nervous, musculoskeletal, and vascular systems. Numerous reviews dealing with vitamin E deficiencies in man have been Generally, the function of vitamin E falls into one of two different metabolic roles-first, as a fat-soluble antioxidant; and second, in one or more specific roles related to the metabolism of selenium and sulfur amino acids. The term “vitamin E” has been loosely described as that group of toco and tocotrienol derivatives possessing varying degrees of vitamin activity. The most active of these, Ntocopherol, is the main subject of this presentation, which involves its usefulness in preventing nitrosamine formation. In this role, vitamin E most appropriately falls into the category of fat-soluble antioxidant. Antioxidants play an important role in the diet as well as in vivo toward preventing undesirable and potentially dangerous reactions from being initiated. In fact, in recent years much emphasis on the role of the chemical and biological environment in carcinogenesis has emerged with the suggestion that the majority of all human cancers may be environmentally related. Further weight has been added to this idea with the identification of many carcinogenic substances, such as polynuclear aromatic hydrocarbons, nitrosamines, aflatoxins, etc., in the human environment. Many of these have been found to be present in the diet. One major class of compounds that has been of concern are the nitrosamines. For the most part, they are highly potent animal carcinogens and generally considered potential human carcinogens. Before discussing the mechanism by which vitamin E is capable of preventing nitrosamine formation, it is important to review some aspects of how nitrosamines themselves are formed.

Bioefficient Products a Novel Delivery System

AbstractStudies have shown that a bioefficient/HBS™ dosage form is more bioavail able than the conventional product. This is true with compounds which are absorbed from the upper portion of the small intestine or intended to act in the stomach contents. The increase in bioavailability is due to the design of this delivery system which is based on the HBS™ having a prolonged retention in the stomach, as shown by scintillation studies. Vitamins evaluated in these experiments include riboflavin, thiamine and a vitamin C plus E combination product.

Antioxidants as Blocking Agents Against Nitrosamine Formation

N-nitroso compounds have been known since they were first synthesized in Germany in the mid-nineteenth century. They have been extensively used in organic synthesis, analytical chemistry and 1 research for over a century. However, in 1954, Barnes and Magee found that dimethylnitrosamine (DMN) produced liver toxicity in two men in the UK. Similarly, an outbreak of acute liver toxicity in sheep in Norway was traced to the formation of DMN in fish meal preserved by nitrite.2 These events prompted the early synthetic investigations of the N-nitroso compounds, particularly by groups headed by Magee in the UK and US, and Druckrey in Germany. Their work, and that of others, rapidly showed that the N-nitroso compounds, as a group, had enormous potential for carcinogenesis. This, in turn, has led to the current deep scientific interest in the analysis, formation, and occurrence of carcinogenic N-nitroso compounds in our food supply, polluted atmosphere, drinking water, beverages, cigarette smoke, cosmetics, industrial waste and by-products, and more recently to their formation in vivo.3,4,5 It is the intention of this paper to survey several aspects of these studies and address the use of ascorbic acid and alpha-tocopherol as blocking agents to prevent the formation of these potential human carcinogens.