Genetic risk assessment and specific-locus mutations in the ad-3 region of Neurospora crassa

Abstract

Data from experiments on the induction of specific-locus mutations in model systems are used 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: a) spontaneous and induced forward-mutation frequencies, b) dose-response curves for the overall induction of specific-locus mutations, c) genetic characterization of spontaneous and induced mutations, and d) dose-response curves for the different genotypic classes. Specific-locus assays in most eukaryote assay systems provide only portions of the information required for such assessments. In recognition of the need for more detailed information for risk assessment, a model system has been developed for specific-locus assays in Neurospora crassa. The adenine-3 (ad-3) specific-locus assay was modeled after the two-gene morphological specific-locus assay in the dilute-short-ear region of the mouse and detects forward-mutations at two closely linked loci: ad-3A and ad-3B. A computerized data management program has made it possible to obtain precise dose-response curves not only for the overall induction of ad-3 mutations, but also for various genotypic subclasses. In addition, computerized statistical programs have been developed to compare dose-response curves. These methods of analysis have shown that the overall dose-response curve for specific-locus mutations in the ad-3 region is a composite of many different genotypic subclasses. In addition, these subclasses may have very different induction kinetics from those of the overall dose-response curve for ad-3 mutations.