Nakahara memorial lecture. Application of the mechanisms of nutritional carcinogenesis to the prevention of cancer.

Historically, the field of experimental chemical carcinogenesis began in Japan with Yamagiwa and has been a traditional subject of study since that time. In Prof. Nakahara's lifetime, he and his disciples have contributed much to an understanding of the basic mechanisms of carcinogenesis. Most types of human cancer are likely associated with chemical carcinogens. In part, we understand the mechanisms whereby carcinogens lead to neoplasia. The overall process involves agents with distinct properties, 1) those modifying the genome with specific consequences, and 2) those controlling the growth and development of latent tumor cells with such an abnormal genome. The genotoxic pathway and the subsequent promoting process proceed by distinct mechanisms and thus have different consequences as regards health risk, especially with respect to dosage and time requirements for effective carcinogenesis. Through multidisciplinary approaches, it has been established that cancer of the stomach and esophagus, prevalent in certain parts of the world, depend on the presence in salted, pickled, or smoked foods of specific chemicals, that are genotoxic and the structure of which is a function of local conditions. Salt can have a cocarcinogenic or promoting role. In much of the Western World, cancers of the colon, pancreas, breast, ovary, endometrium, and prostate are linked to nutritional traditions. The genotoxic carcinogens for several of these neoplasms may be formed during cooking, especially broiling or frying. There is evidence for extensive promoting process, in turn, a function of the total dietary fat intake, through partially understood mechanisms. Additional modifying factors include cereal (bran) fiber, but perhaps not other types of fibers, that reduce the risk for colon cancer. Further modifying elements are discussed in this Symposium. Fair understanding has been achieved of the underlying basic mechanisms, relative to the formation of carcinogens during food preparation and processing, and on the role of certain promoting or inhibiting elements such as fat, fiber, or components of fruits and vegetables. Certain of these elements are sufficiently well established for application to the prevention of specific cancers in various parts of the world.