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Dose-response relationship of specific locus mutations in mice

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Abstract

A linear dose-response relationship is typical for radiation induced specific locus mutations in mice. Departure from a linear dose-effect curve was observed after a low dose of 50 R in female mice and after fractionation of the dose in female and male mice. The mutation frequency after repeated exposure depends both on size of each dose and on spacing of doses. Furthermore, the mutation rate of spermatogonia drops significantly below a linear relationship with dose after X-irradiation with 1,000 R (80 to 90 R/min).

Interperitoneal injection of sublethal doses of mitomycin C (MC) and tretamin (TEM) increased significantly the rate of specific locus mutations in spermatogonia of mice. These data indicate a correlation between dose and mutation frequency. It is suggested to use the specific locus method for an experimental approach to test the threshold concept of chemical agents for mutagenicity in mammals.

Zusammenfassung

Eine lineare Dosis/Wirkungs-Beziehung ist typisch für strahleninduzierte spezifische Lokusmutationen bei Mäusen. Abweichungen von der linearen Dosis/Wirkungs-Kurve wurden nach einer Bestrahlung weiblicher Mäuse mit 50 R und nach fraktionierter Bestrahlung von weiblichen und männlichen Mäusen beobachtet. Die Mutationsrate bei wiederholter Bestrahlung ist abhängig von der Größe jeder Dosis und von der zeitlichen Folge der Dosen. Nach Röntgenbestrahlung mit 1,000 R (80–90 R/min) ist die Mutationshäufigkeit in Spermatogonien kleiner als der Extrapolationswert, der aufgrund einer linearen Dosis/Wirkungs-Beziehung ermittelt wurde.

Eine intraperitoneale Injektion einer subletalen Dosis von Mitomycin C (MC) und Tretamin (TEM) erhöht signifikant die Häufigkeit von spezifischen Lokusmutationen in Spermatogonien von Mäusen. Diese Ergebnisse deuten eine Abhängigkeit der Mutationshäufigkeit von der Dosis an. Es wird vorgeschlagen, mit Hilfe der spezifischen Lokusmethode, das Konzept einer Wirkungsschwelle für die Mutationsauslösung von chemischen Agentien bei Säugetieren experimentell zu prüfen.

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Ehling, U.H. Dose-response relationship of specific locus mutations in mice. Arch. Toxicol. 32, 19–25 (1974). https://doi.org/10.1007/BF00334608

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