Evidence for the re-establishment of a heterogeneity in radiosensitivity among spermatogonial stem cells repopulating the mouse testis following depletion by X-rays.

Earlier studies have shown that the spermatogonial stem cells of the mouse testis recovering from previous radiation or chemical mutagen exposure give subnormal yields of genetic damage with subsequent X-irradiation. This response has been investigated further: (a) with a high, 9-Gy X-ray dose given 4, 12 or 21 days after a 1-Gy conditioning dose (Expt. 1), and (b) with a 1 + 7-Gy, 24-h fractionation regime given 4 or 14 days after a 1-Gy conditioning dose (Expt. 2). In Expt. 1 the 1 + 9-Gy, 4-day interval regime gave a very low response, lower than obtained previously with an equivalent 1 + 5-Gy treatment. This suggests that a heterogeneity in radiosensitivity, such as exists in unirradiated stem cell populations and absent 24-48 h after radiation depletion, is quickly re-established among the stem cells repopulating the testis. By contrast, the 1 + 7-Gy, 24-h fractionation when given 4 days after the 1-Gy conditioning dose (Expt. 2) gave a very high yield of genetic damage, almost as high as that given by the fractionated (1 + 7 Gy) dose applied to previously unirradiated stem cells. This suggests that the newly established heterogeneity is removed by the second 1-Gy conditioning dose. With longer intervals between treatments, genetic yields consistent with additivity were obtained in Expt. 1; less clear results were obtained Expt. 2. Comparison with earlier data generally suggested that the duration of the repopulating period is dose-dependent. In a third experiment evidence was obtained that genetic damage induced by X-irradiation can be reduced by a subsequent treatment with triethylenemelamine (TEM) during the repopulating phase. This confirmed an earlier finding. Such an interaction could not be demonstrated with two X-ray treatments. An explanation for the X-ray/TEM interaction is offered.