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II. Haploid assay systems and overall response of all systems A report of the U.S. EPA gene-tox program

1982; Elsevier BV; Volume: 98; Issue: 1 Linguagem: Inglês

10.1016/0165-1110(82)90003-3

1872-9347

Barry R. Scott, Gordon L. Dorn, Etta Käfer, Robert Stafford,

Mycotoxins in Agriculture and Food

The status of the Aspergillus systems, with respect to their usefulness in screening chemicals for genotoxic effects, was evaluated using information available in the open literature. A total of 179 references were evaluated; 58 contained relevant information for the purpose of determining the genotoxic status of a chemical. To simplify presentation, these papers were divided into two groups. The first group of papers analyzed the effect of chemicals on mitotic segregation in Aspergillus (reported in Käfer et al., this issue). The second group of papers, reporting on the response of the haploid Aspergillus systems to various agents, are reviewed in this paper which also contains an overall summary of the responses of an Aspergillus system and compares these results with those obtained from in vivo carcinogenicity studies. The publications reporting on haploid mutational systems fall into one of three main systems. The methionine suppressor system, the 2-thioxanthine system, and the arginine system. The first two systems are multiallelic forward-mutational systems that respond to agents inducing base-pair changes and small deletions. No report on the nature of the reverse mutations in the arginine system could be found in the literature, although the spontaneous reversion rate would indicate intra-locus reversion rather than forward mutation at suppressor loci as is the case for the methionine assay. Adequate numerical information for 124 chemicals is available from all the acceptable Aspergillus papers listed at the Environmental Mutagen Information Center, Oak Ridge National Laboratory (1965–1978). For 27 of these compounds, corresponding animal bioassays for carcinogenesis were available. The same response in 95% of the chemicals was obtained with both eukaryotic bioassays. 2 of these responses were negative; the remaining 23 were positive for both types of tests. Of the 23 positive responses, 2 required metabolic activation. 5 of the compounds giving positive responses in Aspergillus systems and the carcinogenicity bioassays were not mutagenic for Salmonella. The general conclusion of the working group was that a combination of the simple haploid mutational system, coupled with the uniqueness of diploid analysis, depicts the true value of Aspergillus nidulans for both screening and in-depth analysis of genotoxic chemicals (effects on genes, chromosomes, and “machinery” associated with their segregation).