Comparison of the Mutagenicity and Mutagen Specificity of Ethylenimine with Triethylenemelamine in the Ad-3 Region of Heterokaryon-12 of Neurospora-Crassa

Details

• Personal Author:
  Deserres FJ ; Malling HV ; Ong TM
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Genetics Mutagens Occupational Health Safety
• Keywords:
  Ad-3 Region Ad-3a Locus Ad-3B/Ad-3A Ratio Ad-3b Locus Author Keywords: Heterokaryon 12 Biological-effects Biological-monitoring Carcinogenicity Cell-biology Cell-differentiation Cell-function Cell-metabolism Cell-transformation Cellular-reactions Chemical-properties Chemical-reactions Ethylenimine Gene Point Mutation Genes Genetic-factors Genotoxic-effects Genotoxicity Immune-system Immunotoxins Mulitlocus Deletion Mutation Multiple-locus Mutation Mutagenesis Mutagenicity Mutation Recessive Lethal Mutation Statistical-analysis Triethylenemelamine

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• ISSN:
  1386-1964
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  193-205
• Volume:
  328
• Issue:
  2
• NIOSHTIC Number:
  nn:20035628
• Citation:
  Mutat Res Fundam Mol Mech Mutagen 1995 May; 328(2):193-205
• Contact Point Address:
  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
• Email:
  deserres@niehs.nih.gov
• CAS Registry Number:
  Ethylamine (CAS RN 75-04-7)
• Federal Fiscal Year:
  1995
• Peer Reviewed:
  True
• Source Full Name:
  Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0bc4b4344f7277ad16ee4ae29730f71c95a00988ac013fea4b9ff04273dceea8f02b3839b39210cf6675e3b0930da2f2cc27b593da31a43b9bed78bad085de7f
• Download URL:
  https://stacks.cdc.gov/view/cdc/187425/cdc_187425_DS1.pdf
• File Type:
  [PDF - 1.04 MB ]