Modified genetic response to X-irradiation of mouse spermatogonial stem cells surviving treatment with TEM

Abstract

Earlier studies have shown that the genetic response to X-irradiation of mouse spermatogonial stem-cell populations that are recovering from a previous radiation exposure may differ from that of a normal, unirradiated stem-cell population. Similar modified responses to X-irradiation have now been observed in stem spermatogonia that are recovering from treatment with the chemical mutagen, TEM. (1) In contrast to a normal response to 900 R, high translocation yields were obtained when this dose was administered 24 h after a TEM treatment. (2) A small but non-significant increase above a normal response to 500 R was obtained when this dose followed 24 h after TEM treatment and a normal response to 500 R was obtained from the reverse order treatment (500 R + TEM). (3) When given 4 days after a TEM treatment the translocation yield from 500 R was only about half that normally obtained. Unexpectedly, a similar low response was obtained from the reverse order treatment which, if verified, would suggest selective cell killing by the TEM. The chemical administered alone, was almost totally ineffective in producing recoverable translocations in stem spermatogonia. Since it is unlikely that TEM and X-rays should similarly synchronize the cell cycle of surviving stem spermatogonia it is concluded that the modified genetic responses obtained result from a different cause. Depletion of the stem-cell population is suggested as the common mediating factor. This may “trigger” the radio-resistant, long cycling stem cells into a more active cycle such that, 24–48 h later, survivors may be highly “synchronized” into either a sensitive cell-cycle stage or transient state preparatory to entering a shorter cell cycle to achieve repopulation. The low translocations yields obtained with longer intervals between treatments may typify the genetic response of the repopulating stem cells.