Antimutagenesis and anticarcinogenesis, from the past to the future.

Observations on cancer causation are some 150 years old, but actual detailed research on elements bearing on cancer started at the beginning of the twentieth century. Rapid progress, however, is only some 40 years old. Studies in humans documented certain lifestyle related factors to lead to cancer, and research in animal models strengthened this information. With the realization that there are carcinogens that in a metabolically activated attack DNA, in contrast to other agents that act by promoting, enhancing processes through totally distinct mechanisms, it became possible to develop and apply tests for DNA reactivity, in a prokaryotic organism, the widely used Salmonella typhimurium test by Ames and in a eukaryotic system, namely freshly explanted liver cells displaying evidence of DNA repair by Williams. A battery of these two tests are over 90% accurate in defining genotoxicity. Virtually all documented human carcinogens are genotoxic. With advances in molecular biology, mutational events are traced to changes in tumor suppressor genes or in oncogenes, that can serve as markers of risk. In addition, reactive oxygen systems (ROS) are involved in both the early steps in cancer and in the developmental aspects. Thus, foods containing antioxidants such as vegetables, fruits, soy products, cocoa and tea that counteract ROS are protective in cancer causation and development. Worldwide application of current knowledge and mechanisms to cancer prevention, the definitive means of cancer control, is likely to lower not only cancer but also heart disease risk in the current century.