The mutagenic activity of ethylnitrosourea at low doses in spermatogonia of the mouse as assessed by the specific-locus test.
Ethylnitrosourea is the most efficient chemical mutagen in spermatogonial stem cells of the mouse and its mutagenic activity has been intensively studied. The pertinent specific-locus mutation test results for a discussion of low dose-effect studies have been summarized and indicate: (1) A threshold dose response best characterizes the relationship between dose and mutation rate. (2) The reduced effectiveness of ethylnitrosourea in the low dose range is likely due to a saturable repair process. (3) The recovery of the saturable repair process as assessed in fractionated dose experiments is long (ca. 168 h). The dynamics of stem cell spermatogonia suggests a long time interval before the cell population passes through at least one cell division and this may be relevant to an interpretation of the fractionation effects. (4) There is a slight but important discrepancy between the predicted and observed mutagenic activity of ethylnitrosourea in the low dose range. This is interpreted to be due to the differences between a mathematical abstraction and the biological realities of the system being studied.
Favor
J
J
Institute of Mammalian Genetics, GSF-Research Center for Environment and Health, D-85758, Neuherberg, Germany. favor@gsf.de
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D010641:Phenotype; D013093:Spermatogonia
D009153:Mutagens; D005038:Ethylnitrosourea