The detection of genotoxic activity and the quantitative and qualitative assessment of the consequences of exposures.
A wide range of assays are now available which enable the effective detection of the mutagenic (the induction of gene and chromosomal changes) and more generally genotoxic (cellular interactions such as DNA lesion formation) activity of individual chemicals and mixtures. However, when genotoxic activity has been detected and human exposure occurs the critical questions relate to the qualitative and quantitative activity of the agent and the parameters such as routes of exposure, target organs and metabolism. Of major importance in hazard and risk estimation is the nature of the dose response relationship of each chemical and their potential interactions in mixtures. In this paper, we illustrate the methods available to produce quantitative and qualitative data in vitro using the micronucleus assay (as a measure of chromosomal structural and numerical mutations) and the HPRT assay (as a measure of induced gene and point mutations) and the current limitations (such as the large numbers of animals required) for obtaining such information in vivo. We recommend that in vivo studies should primarily focus upon confirmatory mechanistic analysis. For individual chemicals, profiles of the base changes induced can be obtained using the HPRT gene mutation assay and comparisons produced both in vitro and in vivo and thus allow identification of mechanistic differences between different modes of exposure.
Parry
James M
JM
Centre for Molecular Genetics and Toxicology, Biological Sciences, University of Wales Swansea, Swansea SA2 8PP, UK. JMP@Swansea.ac.uk
Parry
Elizabeth M
EM
Johnson
George
G
Quick
Emma
E
Waters
Eileen M
EM
D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000145:classification / Q000633:toxicity*; D009154:Mutation; D051381:Rats; D018570:Risk Assessment
D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase