Characteristics of spontaneous and induced specific-locus mutation in the ad-3 region of Neurospora crassa: utilization in genetic risk assessment. 1992

F J de Serres
Center for Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, North Carolina 27709.

Data from experiments on the induction of specific-locus mutations in model systems are utilized in genetic risk assessment to estimate potential adverse effects in the human population. In such assessments with radiation or chemical mutagens, the following information is required: (1) spontaneous and induced forward-mutation frequencies, (2) dose-response curves for the overall induction of specific-locus mutations, (3) genetic characterization of spontaneous and induced mutations, and (4) dose-response curves for the different genotypic classes. Specific-locus assays in most eukaryote assay systems provide only portions of the information required for genetic risk assessment. In recognition of the need for a more comprehensive data base, a model system was developed for specific-locus studies in Neurospora crassa. The adenine-3 (ad-3) specific-locus assay was modeled after the 2 gene, morphological specific-locus assay in the dilute-short-ear region of the mouse, and it detects forward-mutations at two closely linked loci: ad-3A and ad-3B. The ad-3 assay system has provided precise dose-response curves not only for inactivation, but also the overall induction of ad-3 mutations. The utilization of this assay in experiments with radiation or chemical mutagens has provided a data base on the induction and genetic characterization of specific-locus mutations that is unique among eukaryotic organisms. In this assay, gene/point mutations, multilocus deletion mutations, and 3 different classes of multiple-locus mutations can be identified. The latter consist of specific-locus mutations associated with recessive lethal mutations located either closely linked to the ad-3 region or elsewhere in the genome. The overall data base on the heterozygous effects of X-ray-induced ad-3 mutations demonstrates that such effects are allele specific, genotype specific, and locus specific. There are probably a variety of mechanisms by which the heterozygous effects of individual allelic mutations at different genetic loci can be affected. In conclusion, unless the frequencies of all of the different classes of induced specific-locus mutations are determined, and utilized in genetic risk assessment exercises, the risk of human exposure to environmental mutagens may be grossly underestimated.

UI MeSH Term Description Entries
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009492 Neurospora crassa A species of ascomycetous fungi of the family Sordariaceae, order SORDARIALES, much used in biochemical, genetic, and physiologic studies. Chrysonilia crassa
D011848 Radioactive Pollutants Radioactive substances which act as pollutants. They include chemicals whose radiation is released via radioactive waste, nuclear accidents, fallout from nuclear explosions, and the like. Pollutants, Radioactive
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D004271 DNA, Fungal Deoxyribonucleic acid that makes up the genetic material of fungi. Fungal DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D004785 Environmental Pollutants Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS. Environmental Pollutant,Pollutant,Pollutants,Pollutants, Environmental,Pollutant, Environmental

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