Aneuploidy as a human health problem of significance in environmental mutagenesis.

The Workshop on Systems to Detect Induction of Aneuploidy by Environmental Mutagens was organized to fulfill several needs. The most pressing need is to provide a capability that can be used in screening programs involving tests on thousands of untested environmental chemicals. None of the assay systems currently proposed for use in these screening programs can detect chemicals producing aneuploidy by nondisjunction or any other mechanisms. It is essential to have the capability to detect those chemicals whose sole genetic effect may be the induction of aneuploidy as well as those chemicals which induce aneuploidy along with other types of genetic damage such as gene mutations and chromosome aberrations. The differences between prokaryotic and eu-karyotic organisms, with regard to chromosome structure (DNA versus nucleoprotein) and behavior during cell division, effectively limits assay system development to eukaryotes. Even among eukary-otes, differences in chromosome structure both with regard to histone and nonhistone proteins as well as the organization of the DNA (relative frequencies of repetitive versus nonrepetitive sequences) may confer a specificity that will make extrapolation from lower eukaryotes to higher eukaryotes difficult if not impossible. We do not know how serious these problems will be on the basis of present data, but because of the urgency of this problem, we must make a start towards test system development even in the absence of such knowledge. In this workshop we have attempted to make a coordinated evaluation of these and related problems with regard both to the initial detection of chemicals which can cause aneuploidy, as well as, the additional assays that would be required for informed risk estimation. A review of the data in papers available in the open literature shows that relatively few assay systems have been developed with this genetic endpoint in mind, and that the number of chemicals which have been tested in those assay systems is quite limited. In the strictest sense, this workshop is intended as a beginning in the process of stimulating research in a somewhat neglected area of environmental mutagenesis. There is little doubt in our mind concerning the necessity to limit human exposure to chemicals that would cause this type of genetic damage in the human population. Even in the absence of a comprehensive data base with regard to the incidence of various syndromes resulting from aneu-ploidy on a worldwide basis, the effects of aneu-ploidy in the human population are well known. Downs' …