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Proc Natl Acad Sci U S A. Oct 1985; 82(19): 6619–6621.
PMCID: PMC391261

Dose-repetition increases the mutagenic effectiveness of N-ethyl-N-nitrosourea in mouse spermatogonia.


In order to maximize the mutagenic effectiveness of N-ethyl-N-nitrosourea in mouse stem-cell spermatogonia, advantage was taken of the fact that these cells can accumulate mutations from repeated doses given over relatively long time periods. Repeated doses (100 mg/kg) of ethylnitrosourea injected intraperitoneally into male mice at weekly intervals were found to allow adequate survival and fertility with total dosages of 300 and 400 mg/kg. The specific-locus mutation frequencies at these dosages were, respectively, 1.8 and 2.2 times that obtained with the maximal practicable single dose of 250 mg/kg. The mutation frequency induced by a 400 mg/kg dosage of ethylnitrosourea is 12 times the maximal mutation frequency achievable with a single exposure to x-rays and 36 times that reported for procarbazine, the most effective chemical mutagen previously known for mouse stem-cell spermatogonia. Ethylnitrosourea is already the mutagen of choice in deliberate attempts to create mouse models for human disease and in any experiments in which a maximal mutation rate is desired. Repeated-dose regimens similar to the ones reported here should increase the efficiency of such studies.

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Selected References

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  • Russell WL, Kelly EM, Hunsicker PR, Bangham JW, Maddux SC, Phipps EL. Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5818–5819. [PMC free article] [PubMed]
  • Russell WL, Hunsicker PR, Raymer GD, Steele MH, Stelzner KF, Thompson HM. Dose--response curve for ethylnitrosourea-induced specific-locus mutations in mouse spermatogonia. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3589–3591. [PMC free article] [PubMed]
  • Goodfellow PN. Of man and mouse. Nature. 1985 Mar 14;314(6007):135–135. [PubMed]
  • RUSSELL WL. X-ray-induced mutations in mice. Cold Spring Harb Symp Quant Biol. 1951;16:327–336. [PubMed]
  • Selby PB, Niemann SL. Non-breeding-test methods for dominant skeletal mutations shown by ethylnitrosourea to be easily applicable to offspring examined in specific-locus experiments. Mutat Res. 1984 Jun;127(1):93–105. [PubMed]
  • Ehling UH, Neuhäuser A. Procarbazine-induced specific-locus mutations in male mice. Mutat Res. 1979 Feb;59(2):245–256. [PubMed]

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