MUTAGENICITY SCREENING WITH FUNGAL SYSTEMS

Abstract

Several fungal species have been used for mutagenicity screening: Aspergillus nidulans, Saccharomyces cerevisiae, and Neurospora crassa. The eukaryotic nature of these organisms with typical chromosomes in a nucleus and their mitotic and meiotic mode of nuclear division have been the basis for the development of test systems that cover the full spectrum of genetic changes typical for eukaryotes. It is possible to detect simple point mutations and also grosser structural chromosomal alterations. Mitotic recombination as a repair test has found wide application. In recent years, the induction of mitotic and also meiotic chromosomal malsegregation has been investigated. It turned out that there are numerous chemicals that specifically induce only aneuploidy but no other type of genetic change. Among such chemicals are well-known tumor promoters, membrane-active agents, and others that have been shown to interact with tubulin and interfere with microtubule formation and function in mammalian cells. Such agents will be classified as nonmutagenic in any of the presently used mutagenicity test batteries, which monitor only changes that result from primary effects exerted either directly on DNA or indirectly via interference with DNA metabolizing enzymes. Consequently, fungal tests for induction of aneuploidy do not represent an optional alternative to other tests, but they are a mandatory part of any test battery aimed at uncovering all kinds of mutagenic agents.