The response of spermatogonial stem cells to fractionated X irradiation was studied in the various stages of the spermatogenic cycle of the CBA mouse. Fractionated doses of 2 + 2, 1 + 3, and 3 + 1 Gy with a 24-h interval between the doses were compared with a single dose of 4 Gy. The numbers of undifferentiated spermatogonia present 10 days after (the second) irradiation were taken as a measure of stem cell survival. Twenty-four hours after the first irradiation a sensitization was observed that was found to be stage-dependent. The greatest sensitization occurred in that part of the spermatogonial stem cell population that was in stages X-I during the first irradiation, i.e., the part that is stimulated to proliferate or actively proliferating at that time. In stages that were quiescent during the first irradiation (VI-VII), fractionation did not influence the response. Therefore, only the spermatogonial stem cells that are initially radioresistant become sensitized 24 h after irradiation. When two unequal doses (3 + 1 Gy or 1 + 3 Gy) are given, damage correlates with the size of the second dose, indicating that priming doses of 1 and 3 Gy are both capable of inducing the sensitizing effect.

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