MUTATIONAL SPECIFICITY AND CANCER CHEMOPREVENTION

Mutational specificity describes the composite of all of the genetic a lterations in a collection of mutations arising from a specific treatm ent. The information includes not only the nature of the genetic chang e (e.g., a base substitution or a frameshift), but also information ab out nucleotide position and hence the DNA context. As both the type of DNA damage and its position can be expected to reflect the nature of the chemical and physical mutagen, mutational specificity can be expec ted to provide insights into mechanisms of mutation. Conversely, mutat ional spectra should also provide insights into the identity of the mu tagen. Indeed, the pioneering work on mutational specificity in Escher ichia coli indicates that each physical or chemical treatment produces a unique spectrum of mutations. With the application of biotechnology to the field of genotoxicology, the database of sequenced mutations h as become quite substantial. Both in vitro and in vivo data has been o btained following exposure to a variety of agents. In this communicati on we will critically assess whether the reality of mutational specifi city has fulfilled the expectations and to examine what potential rema ins to be explored, especially in the area of monitoring human populat ions. The usefulness of both mutational spectra analysis and populatio n monitoring with regards to chemoprevention are discussed. (C) 1997 W iley-Liss, Inc.