Interactions of Fungal and Plant Toxins with DNA: Aflatoxins, Sterigmatocystin, Safrole, Cycasin, and Pyrrolizidine Alkaloids

Abstract

Since the discovery of the aflatoxins in 1960, much effort has been made by research laboratories to investigate the association between exposure to naturally occurring carcinogens and long-term adverse health effects in people. In the case of aflatoxin B1, these health consequences range from acute hepatic liver toxicities to liver cancer. During the ensuing years, the vast majority of the mechanistic biochemical studies inquiring into the mode of action of naturally occurring chemical carcinogens have been carried out using aflatoxin Bl. In fact, the aflatoxins are among the few ubiquitous and structurally identified environmental carcinogens for which quantitative estimates of human exposure have been systematically sought and risk assessments attempted. However, in the past 10 years compounds such as sterigmatocystin, cycasin, the family of pyrrolizidine alkaloids, and especially safrole and estragole have been more extensively probed. Stimulus for this research has undoubtedly been generated by the hypothesis that prevention of dietary exposure to naturally occurring plant and fungal carcinogens will improve the general health status of a population. Since it is almost axiomatic that the development of human cancer can be modulated by many factors both biological and chemical in nature, and because initiation, promotion, and progression-like events are required prior to the clinical diagnosis of a tumor, no one agent can be responsible for, or present at all the critical stages during the growth of a tumor. Therefore, the systematic investigation of the biological consequences of exposure to dietary carcinogens will help to develop appropriate cancer prevention strategies.