Antimutagen and Anticarcinogen Research in Japan - ACS Publications

Chapter 4

Antimutagen and Anticarcinogen Research in Japan 1

Mitsuo Namiki

Downloaded by UNIV LAVAL on April 8, 2016 | http://pubs.acs.org Publication Date: December 20, 1993 | doi: 10.1021/bk-1994-0546.ch004

Tokyo University of Agriculture, Setagaya-ku, Tokyo 156, Japan, and Nagoya University, Chikusa, Nagoya 464—01, Japan

Marked changes in Japanese food and diet over the past 40 years have resulted in significant elongation of the average life expectancy along with an increase in cancer deaths involving changes in incidence distribution. Following progress in studies on mutagenesis, carcinogenesis and oxygen diseases, studies on antioxidants, antimutagens and anticarcinogens in food are being promoted in Japan as an important part of research in the physiological functionality of food. Various novel physiological activities are being elucidated in Japanese traditional foods, e.g. antimutagenicity of tea catechins, sea weeds and flavoring compounds, antioxidative and antiaging activities of sesame, spices, tea, fermented foods and others. Various oligosaccharides and dietary fibers are being developed to improve colonic microflora correlated to carcinogenesis.

Due to the mild and oceanic climate of the Japanese islands, and perhaps also to Japanese religious and racial features, the Japanese people have developed a unique food culture. Their diet consists of a variety of plants and seafood with rice as the staple food. The use of raw foods (such as raw fish, sushi, seaweeds), many fermented products (including soy sauce, miso, natto, sake, and others), and various salty pickles is particular to the Japanese diet. The Japanese food culture was originally affected by the Chinese belief that daily diet controls health, disease and aging, and has traditionally used various medicinal foods, for example, green tea, sesame seed and oil, sake and rice vinegar, mushroom (shiitake), various seaweeds and other foods. They are believed to chronically affect health and aging, but until recently little work had been done to elucidate their effects using modern chemical and medical methods. Food and Health, Cancer and Aging After the Second World War, the Japanese diet greatly changed in quality and quantity from very poor to saturation. Thus, as shown in Figure 1, the average life 1

Current address: Meito-ku, Yashirodai 2-175, Nagoya 465, Japan

0097-6156/94/0546-0065$06.00/0 © 1994 American Chemical Society

Huang et al.; Food Phytochemicals for Cancer Prevention I ACS Symposium Series; American Chemical Society: Washington, DC, 1993.


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FOOD PHYTOCHEMICALS I: FRUITS AND VEGETABLES

expectancy increased rapidly over the past 40 years (1950-1990), from 50 to 78 years of age for males and 54 to 80 years of age for females. It is now the longest in the world (7). Among many factors to be considered as a reason why such rapid elongation of life expectancy was achieved, first of all, improvement of diet in nutrition and sanitation should be pointed out. The Japanese diet changed from the traditional one to become closer to the U.S.-European type, resulting in increased intake of animal protein and fat and decreased intake of carbohydrate and dietary fiber (Figure 2). At the same time, the pattern of cause of mortality in Japan changed, and since 1981 cancer has become number one (Figure 3). In Japan in 1955, the cancer mortality rate by type was by far the highest in stomach, over 50% for males, then in decreasing order liver, lung, esophagus, colon and other cancers. This is quite different from the U.S.-European countries, where lung, colon, breast and liver cancers are dominant and the stomach cancer rate is low. This apparent difference between Japan and Western countries is thought to be due mainly to differences in diet, i.e. high cereal, fish and salt intake in Japan and high animal fat and meat intake in the U.S.-European countries. In recent years, the mortality ratio in Japan has tended toward the U.S.-European type, that is, a gradual decrease in stomach cancer and increase in lung and colon cancers (Figure 4) (7), probably due to changes in the Japanese diet making it more closely resemble the U.S.-European type. Research Projects on Physiological Functionality of Food Given these circumstances, starting in the 1970's, a new research field has developed in food science in Japan to elucidate the unknown physiological activities of our daily diets, especially those concerning immune response, circulatory diseases, carcinogenesis and aging. These comprehensive studies are conducted in conjunction with advanced medicinal, biochemical and food-chemical investigations. One large project, "Systematic Analysis and Development of Food Functionalities," was started in 1984 with the support of a grant-in-aid from the Ministry of Education, Science and Culture of Japan to Professor M . Fujimaki and 81 collaborating professors (1984-1986) (2). This was continued in two other projects, "Analyses of Body-modulating Functions of Foods" (Professor H. Chiba, 1988-1990) (3) and "Analysis and Molecular Design of Physiologically Functional Foods" (Professor S. Arai, 1992- ). Another project, "Research on Cancer Chemoprevention" was started 1983 within the framework of a Japanese cancer research program supported by the Ministry of Health and Welfare of Japan (4). In these projects and others, research on antioxidants, antimutagens and anticarcinogens in food and related materials are being conducted as important fundamental studies on prevention of cancer and aging. Progress in Environmental Mutagen Research Studies on the effects of food components on mutagenesis and carcinogenesis greatly advanced in the 1970's with the development of rapid and sensitive methods to assay mutagens using microbial mutants, e.g., the rec assay using Bacillus subtilis mutant by Kada (5) and the Ames test using Salmonella typhimurium mutants by Ames (6). Many studies using these assays demonstrated the presence



NAMIKI

Antimutagen and Anticarcinogen Research in Japan

4Q I 1920

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Figure 1. Average life expectancy in Japan (1920-1990). 120 r

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Figure 2. Changes in daily intake of major nutrients in Japan.




Figure 4. Age-adjusted mortality rates of malignant neoplasma in Japan.



4. NAMIKI

Antimutagen and Anticarcinogen Research in Japan

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of a number of mutagens in our environment and gave valuable information on their role in carcinogenesis, leading to the conclusion that food and diet may be the most important factors in chemical carcinogenesis (7). One of strongest impacts caused by this mutagen research concerned the mutagenicity of food additives, especially that of nitrofuran derivatives which have very strong antiseptic activity. They have been widely used as preservatives for various foods in Japan, such as fish, meat sausages and ham, soybean tofu, and red bean jam, especially after the Second World War when the cold chain system of food supply was not yet established. In the early 1970's, Kada pointed out the strong mutagenicity of these additives by microbioassay (£), and after further research on their carcinogenicity, most came to be excluded from the list of food additives permitted by the government. After this, use of food additives became a strong public concern and the trend now is to use as little additives as practical for food preservation. Another impact was the discovery of the so called pyrolysate mutagens, or heterocyclic amine mutagens, by Sugimura et ai (9,10) in pyrolysates of amino acids (Trp-P-1) and in various roasted foods (MelQ). These mutagens showed extraordinarily strong mutagenicity in the Ames test, and it was demonstrated that they are not contaminants but Maillard reaction products formed during roasting and broiling of various foods. These facts provided not only an important subject of chemical carcinogenesis research but also had a strong social impact in the daily diet once it was suggested that they are an important factor in the high incidence of stomach cancer among the Japanese people. Antimutagens in Food and Related Materials At about the same time, Kada discovered suppressive activity against heterocyclic amine mutagens as Trp-P-1 in various vegetable juices, including cabbage, broccoli and burdock (77). After investigations on the action mechanisms of various agents suppressing mutagenicity, Kada proposed that antimutagens be divided into two types, "desmutagens" and "bio-antimutagens" (72). As shown in Figure 5, the former are concerned in various ways with the prevention of D N A damage in cells, as explained in the following subsection. The latter act in the processes of muta genesis of the DNA-damaged cells, and the effect mostly involves enhancement of repair and suppression of repair error. Desmutagenesis Research in Japan. Recent studies on desmutagens in food system in Japan can be summarized according to their assumed mode of action. Inhibition of Mutagen Formation. Inhibition of mutagen formation is the first step of desmutagenesis and the effects of ascorbic acid, α-tocopherol and cysteine against nitrosamine formation are well known (13-15). Recently, scorbamic acid, an amino-carbonyl reaction product of dehydroascorbic acid with amino acid, was shown to eliminate nitrite more effectively than ascorbic acid (16). Phenolic compounds are also known to inhibit nitrosamine formation, as observed in the cases of sesamol, an antioxidative phenolic compound formed from sesamolin (77), and B H A (18). When considering these eliminating effects, how ever, it must be noted that they are markedly influenced by pH and the compounds sometimes act as promoters of the formation and also provide other types of mutagens.


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As mentioned above, heterocyclic amine mutagens such as IQ are a kind of Maillard reaction product but its common product melanoidin was shown to inhibit nitrosamine formation, probably due to reduction of nitrite by melanoidin (79). Direct Chemical Inactivation of Mutagens. Chemical inactivation has been observed in the case of the metabolically active products of M N N G and TrpP-1 by green and black tea extracts as well as tea catechins (20). This result is of interest because of an epidemiological report showing that stomach cancer inci dence in a tea producing area is lower than in other areas in the Shizuoka prefecture of Japan (27). Oolong tea extract has also shown to suppress chromosome aberrations induced by benzo[

Antimutagen and Anticarcinogen Research in Japan - ACS Publications

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