IS POLYPLOIDY AN IMPORTANT GENOTOXIC LESION

The importance of polyploidy as a genotoxic lesion is uncertain and th ere have been few publications and no reviews which have included data on spontaneous or induced polyploidy in routine genotoxicity screenin g. We have attempted to clarify some of the issues by reviewing the pu blished literature and by reference to our historical data base for me taphase analysis of cultured human lymphocytes. In our studies on phar maceutical compounds polyploidy was the lesion most often found, being induced by -40% of the compounds tested. The mean spontaneous frequen cy was between 0.1 and 0.3%, and values for polyploidy induction were 5-fold to >100-fold the spontaneous value. Spontaneous polyploids tend ed to be near-exact multiples of the haploid chromosome number whereas induced 'polyploids' were, in fact, very heteroploid with a wide rang e of chromosome numbers. Polyploidy induction often occurred at non-to xic concentrations, usually there were well defined no-effect (thresho ld) levels and it was unrelated to other genetic effects. Such observa tions would be expected for inducers of polyploidy because the target molecules are not DNA and for these non-DNA targets there is usually a degree of redundancy. Therefore, inducers of polyploidy are only like ly to be a hazard for humans if they are positive at or below therapeu tic concentrations. We conclude that polyploidy/near-polyploidy (shown as 'polyploidy' throughout) should be scored as accessory data which becomes important only when induction occurs at therapeutic levels.