Comparison of the mutagenicity and mutagen specificity of ethylenimine with triethylenemelamine in the ad-3 region of heterokaryon-12 of Neurospora-crassa.
Deserres-FJ; Malling-HV; Ong-TM
Mutat Res Fundam Mol Mech Mutagen 1995 May; 328(2):193-205
Studies have been performed to compare the mutagenicity and mutagenic specificity of the trifunctional alkylating agent, triethylenemelamine (TEM), and a closely related monofunctional agent, ethylenimine (EI), in the adenine-3 (ad-3) region of a 2-component heterokaryon (H-12) of Neurospora crassa. The primary objective of our studies was to characterize the genetic damage produced by each agent with regard to (1) mutagenic potency, and (2) the spectrum of specific-locus mutations induced in a lower eukaryotic organism. As in higher eukaryotes, specific-locus mutations in the ad-3 region of H-12 result from gene/point mutations, multilocus deletion mutations, and multiple-locus mutations. Specific-locus mutations resulting from gene/point mutation and multilocus deletion mutation can be detected in higher eukaryotes, but multiple-locus mutations can be detected only with difficultly or not at all. Our experiments with the ad-3 forward-mutation assay have demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) and EI is a moderate mutagen (maximum forward-mutation frequency between 10 and 100 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Classical genetic tests were used to identify the different genotypic classes and subclasses among the EI- and TEM-induced ad-3 mutations from each experiment. The overall data base demonstrates that both EI- and TEM-induced ad-3 mutations result predominantly from gene/point mutations at the ad-3A and ad-3B loci (97.3% and 95.5%, respectively), and infrequently from multilocus deletion mutations (2.7% and 4.5%, respectively). Heterokaryon tests for allelic complementation on TEM- and EI-induced ad-3B mutations, however, have revealed a difference between the percentages showing allelic complementation (63.1% and 40.9%, respectively). Based on the specific revertibility of complementing and noncomplementing ad-3B mutations induced by other agents, this difference in the percentages of ad-3B mutations showing allelic complementation results from a difference between the spectrum of genetic alterations at the molecular level. In addition, comparison of the ratio of TEM-induced ad-3A and ad-3B mutations with those induced by EI has revealed a difference between the ad-3B/ad-3A ratios.
Biological-effects; Biological-monitoring; Carcinogenicity; Cell-biology; Cell-differentiation; Cell-function; Cell-metabolism; Cell-transformation; Cellular-reactions; Chemical-properties Chemical-reactions; Genes; Genetic-factors; Genetics; Genotoxic-effects; Genotoxicity; Immune-system; Immunotoxins; Mutagenesis; Mutagenicity; Mutagens; Mutation; Statistical-analysis;
Author Keywords: heterokaryon 12; gene point mutation; multiple-locus mutation; mulitlocus deletion mutation; ad-3 region; ad-3a locus; ad-3b locus; recessive lethal mutation; triethylenemelamine; ethylenimine; ad-3B/ad-3A ratio
Frederick J. deSerres, Toxicology Branch, Environmental Toxicology Program, Division of Intramural Research, National institute of Emironmental Health Sciences, MD 19-02, P.O. Box 12233, Research Triangle Park, NC 27709-2233
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis