Mutational specificity and cancer chemoprevention.
Mutational specificity describes the composite of all of the genetic alterations in a collection of mutations arising from a specific treatment. The information includes not only the nature of the genetic change (e.g., a base substitution or a frameshift), but also information about 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 expected to provide insights into mechanisms of mutation. Conversely, mutational spectra should also provide insights into the identity of the mutagen. Indeed, the pioneering work on mutational specificity in Escherichia 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 has become quite substantial. Both in vitro and in vivo data has been obtained following exposure to a variety of agents. In this communication we will critically assess whether the reality of mutational specificity has fulfilled the expectations and to examine what potential remains to be explored, especially in the area of monitoring human populations. The usefulness of both mutational spectra analysis and population monitoring with regards to chemoprevention are discussed.
Curry
J
J
Centre for Environmental Health, University of Victoria, British Columbia.
Khaidakov
M
M
da Cruz
A
A
Karnaoukhova
L
L
Kusser
W C
WC
de Boer
J
J
Moffat
J
J
Glickman
B W
BW
D000818:Animals; D030801:Animals, Genetically Modified; D014408:Biomarkers, Tumor / Q000032:analysis; D018890:Chemoprevention / Q000639:trends; D004252:DNA Mutational Analysis; D005047:Etoposide / Q000009:adverse effects; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000032:analysis / Q000235:genetics; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D007041:Hypoxanthine Phosphoribosyltransferase