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.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007248:Infertility, Male / Q000139:chemically induced; D008297:Male; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D009154:Mutation; D011247:Pregnancy; D013093:Spermatogonia / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects; D013997:Time Factors
D009153:Mutagens; D005038:Ethylnitrosourea