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.