Milestones in chemical carcinogenesis.

Abstract

S TUDIES on chemical carcinogenesis had their origin in the findings of unusually high incidences of certain cancers in humans exposed to large amounts of tobacco snuff, coal tar, or aromatic amines. These findings in humans eventually led to extensive laboratory studies on the natures of chemicals that induce cancer in experimental animals and on the mechanisms involved in this process. Although our understanding of chemical carcinogenesis is still limited, the results of laboratory studies are now beginning to be used in the elucidation of the etiologies of cancers in the general human population. Of particular interest is the relationship between the incidences of specific human cancers and exposures to synthetic and naturally occurring environmental chemical carcinogens, and modulators of carcinogenesis. The presentday emphasis on chemical carcinogens as possible major etiologic agents for human cancers derives both from the strong activity that these types of carcinogens can have in animals and humans and from the lack of evidence that known carcinogenic viruses, ionizing radiations, or genetic traits are critical factors in the wide geographic differences in the incidences of most human cancers. Nevertheless, definitive doserelated increases in the incidences of certain human cancers have been associated with exposures to ionizing radiations in excess of background levels.’ Further, there are positive correlations between exposure to hepatitis-B virus and human hepatic cancer2 and between certain herpes-virus infections and cervical cancer, nasopharyngeal cancer, or Burkitt’s lymphoma.3 The following pages contain brief discussions of the major findings or milestones in the studies on chemical carcinogenesis. Although we have tried to be objective in considering the massive literature, our judgments must inevitably contain some subjective elements and may have been further compromised by the space limitation for this article. In general, we have considered the first observations in an area to be “milestones.” Subsequent related observations with other carcinogens or other protocols, even though frequently more extensive, have usually not been included. Likewise, since recent events