van Buul P P, Bootsma A L
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratory, The Netherlands.
Mutat Res. 1994 Dec 1;311(2):217-24. doi: 10.1016/0027-5107(94)90179-1.
To analyze in more detail the relation between the sensitivity of spermatogonial stem cells to killing and the induction of genetic damage, mature male mice received combined treatments with hydroxyurea (HU), 3-amino-benzamide (3-AB) and X-rays. Stem cell killing was determined using the repopulation index method and translocations were studied via spermatocyte analysis. HU was administered at 16 or at 48 h before further treatment in order to create stem cell populations with different sensitivities in which the translocation induction and stem cell killing could be studied and compared. The sensitivities for cell death and genetic damage appeared to be strongly correlated: at 16 h after HU significantly higher values were found than at 48 h or in controls without HU pretreatment. By using 3-AB in the treatment schedules we were able to investigate whether the sensitization of stem cells towards cell death and genetic damage is the outcome of a radiation- or drug-induced G1 delay. The effect of 3-AB was most pronounced at 16 h after HU. This confirms that at this interval a large fraction of stem cells is in G1. Our data therefore indicate that all treatments that induce an enrichment of G1 cells also result in a sensitization of stem cells to cell killing or the induction of mutagenic damage.
为了更详细地分析精原干细胞对杀伤的敏感性与遗传损伤诱导之间的关系，成年雄性小鼠接受了羟基脲（HU）、3-氨基苯甲酰胺（3-AB）和X射线的联合治疗。使用再增殖指数法测定干细胞杀伤情况，并通过精母细胞分析研究易位情况。在进一步治疗前16小时或48小时给予HU，以创建具有不同敏感性的干细胞群体，从而研究和比较易位诱导和干细胞杀伤情况。细胞死亡和遗传损伤的敏感性似乎密切相关：与未进行HU预处理的对照组或48小时时相比，在HU处理后16小时发现的值显著更高。通过在治疗方案中使用3-AB，我们能够研究干细胞对细胞死亡和遗传损伤的敏化是否是辐射或药物诱导的G1期延迟的结果。3-AB的作用在HU处理后16小时最为明显。这证实了在此间隔时大部分干细胞处于G1期。因此，我们的数据表明，所有诱导G1期细胞富集的治疗方法也会导致干细胞对细胞杀伤或诱变损伤诱导的敏化。
