Translocation yield from the mouse spermatogonial stem cell following fractionated X-ray treatments: influence of unequal fraction size and of increasing fractionation interval

(1) The genetic response of the mouse spermatogonial stem cell to a high dose of X-rays given in two unequal fractions 24 h apart can be dependent upon the order in which the two fractions are given. When 1000 R was administered as 100 R followed by 900 R the recovered translocation yield (22%) was similar to that which can be obtained by extrapolation from lower doses and also to that of a 500 + 500 R 24 h fractionation. By contrast, when the 900 R preceded the 100 R the response was much lower (7.4%), yet still greater than that produced by a single 1000 R treatment (4.5%). The same order of effectiveness was observed for length of sterile period. (2) The sub-additive translocation yields previously obtained with 800 R treatments given in fractions of 500 R and 300 R at intervals of 3-12 days were found to be maintained with intervals up to at least 15 days but additivity was regained by the end of the third week. Sterile period data indicated that with these intervals the germinal epithelium had recovered sufficiently from the first fraction for spermatogenesis to restart before the second fraction was given. (3) It is concluded from the two experiments that (a) 24 h after a radiation exposure the surviving stem cells are more sensitive than formerly both to killing and genetic damage, (b) at this time they are no longer heterogeneous in their radiosensitivities, so that increasing yields of genetic damage may be obtained with increasing dose i.e. there is no fall in yield at higher doses, (c) the change in sensitivity could be a consequence of a synchronization to a sensitive stage in a cell cycle, or to a transitional phase preparatory to entering a different cell cycle. (d) to achieve rapid repopulation of the germinal epithelium the surviving stem cells are stimulated to enter a shorter cell cycle and this is the cause of the sub-additive translocation yields with fractionation intervals of 3-15 days, (e) the recommencement of spermatogenesis is associated with the reestablishment of the heterogeneity in radiosensitivity among the stem cells. At this time additive translocation yields can again be recovered.