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Dominant lethal mutations in male mice

Abstract

Dominant lethal mutations are due to chromosome aberrations as demonstrated by analysis of first cleavage. With a sample size of 40–45 mice per dose the induction of dominant lethal mutations by 10 mg/kg of methyl methanesulfonat (MMS) can be detected in spermatids in the mating interval 9–12 days posttreatment (6–11%). In the same mating interval a dose of 150 mg/kg of MMS induces 100% dominant lethal mutations. MMS and other chemical mutagens can be characterized by their different spermatogenic response. The germ cell stage specific induction of dominant lethal mutations by chemical agents is very likely due to their different pathways and therefore, to different effects on the structural and macromolecular changes during spermatogenesis. The feasibility of standardizing test protocol for the dominant lethal assay in mice, based on collaborative studies, is discussed. The reproducibility of results and the sensitivity of the induction of dominant lethal mutations in the collaborative studies demonstrate the usefullness of the method for mutagenicity screening.

Zusammenfassung

Dominante Letalmutationen sind eine Folge von Chromosomenaberrationen, die sich im ersten Teilungsstadium nachweisen lassen. Mit einer Kollektivgröße von 40–45 Mäusen pro Dosis kann die Induktion von dominanten Letalmutationen mit 10 mg/kg Methylmethansulfonat (MMS) in Spermatiden im Paarungsintervall 9–12 Tage nach der Behandlung nachgewiesen werden (6–11%). Im gleichen Paarungsintervall induziert eine Dosis von 150 mg/kg MMS 100% dominante Letalmutationen. MMS und andere chemische Mutagene zeichnen sich durch eine unterschiedliche Wirkung auf verschiedene Keimzellstadien aus. Die keimzellspezifische Induktion von dominanten Letalmutationen ist bedingt durch die unterschiedlichen Wirkungsmechanismen der Mutagene, die verschiedenartige Biosyntheseprozesse blockieren oder verschiedenartige prämutative Schädigungen induzieren. Die Möglichkeiten der Standardisierung des dominanten Letaltestes aufgrund der Erfahrung von Ringversuchen werden diskutiert. Die Reproduzierbarkeit der Ergebnisse und die Empfindlichkeit der Methode in den Ringversuchen beweisen, daß der dominante Letaltest eine sehr brauchbare Methode für die Mutagenitätsprüfung ist.

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Ehling, U.H. Dominant lethal mutations in male mice. Arch. Toxicol. 38, 1–11 (1977). https://doi.org/10.1007/BF00293658

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Key words

  • Dominant lethal mutations
  • Dose-response-relationship
  • Differential spermatogenic response
  • Standardization
  • Mouse