Genetic toxicology: impact on the next generation of toxicology.

Abstract

In the early 1970s, we overestimated the range of applicability of the hypothesis that mutations were highly predictive of rodent cancer. Many substances that are nonmutagenesis in current screens are carcinogenic; some genotoxicants are not carcinogenic. Methods of quantitative risk assessment that were based on the 1970s' hypothesis of cancer induction are thus inherently limited. Current methods of classifying carcinogens and calculation of human risk must reflect recent understanding of the diversity of mechanisms of carcinogenicity. Screening for genotoxic potential has clearly helped to prevent highly toxic and high risk chemicals from being introduced into commerce. Additional attention, however, must now be focused on assessment and management of risk of those carcinogens and other toxicants that cause damage through mechanisms other than direct damage to DNA. While in the past we depended on the knowledge of chemists and genetic toxicologists to predict carcinogenic potential, on whom do we depend today? With the increasing complexity of our knowledge of the processes of carcinogenicity, it is likely that there will not be any single discipline that can meet the challenge. The more we learn, the more we will come to depend on a profile of information that encompasses the known mechanisms of cancer.