Istituto Nacionale de Investigaciones Nucleares, México, DF, México.
Radiat Res. 2010 Mar;173(3):386-91. doi: 10.1667/RR1920.1.
Abstract To establish a basis for a possible strategy for bone marrow ablation or therapy, we examined the effect of bromodeoxyuridine (BrdU) incorporation into DNA on the genotoxic and cytotoxic effects of samarium-153 ethylenediaminetetramethylene phosphonate ((153)Sm-EDTMP) in normoblasts in vivo. Cytotoxicity and genotoxicity were established by time-response curves of polychromatic erythrocyte (PCE) and micronucleated polychromatic erythrocyte (MN-PCE) frequencies, respectively, in mouse peripheral blood samples. The group treated with (153)Sm-EDTMP showed a clear induction of MN-PCEs; however, the group treated with BrdU plus (153)Sm-EDTMP paradoxically showed only a slight increase with respect to untreated controls. Treatment with (53)Sm-EDTMP caused a small reduction in PCE frequency, but exposure to BrdU or to BrdU plus (53)Sm-EDTMP reduced the PCE frequency significantly from 32 h to the end of the experiment. The PCE frequencies in the BrdU plus (53)Sm-EDTMP group were significantly lower than in the BrdU control group at the final time and were much lower than the group treated with only (53)Sm-EDTMP, which returned to basal values. The results suggest the radioinduction of a lethal lesion in BrdU-substituted DNA that cannot be repaired easily and does not permit cell division and micronucleus formation.
为了为骨髓消融或治疗的可能策略建立基础，我们研究了溴脱氧尿苷（BrdU）掺入 DNA 对体内正常红细胞中钐-153 乙二胺四亚甲基膦酸酯（（153）Sm-EDTMP）的遗传毒性和细胞毒性的影响。通过多色红细胞（PCE）和微核多色红细胞（MN-PCE）频率的时间反应曲线分别建立了细胞毒性和遗传毒性。用（153）Sm-EDTMP 处理的组显示 MN-PCE 明显增加；然而，用 BrdU 加（153）Sm-EDTMP 处理的组与未处理的对照组相比，仅显示出轻微增加。用（53）Sm-EDTMP 处理会导致 PCE 频率略有降低，但暴露于 BrdU 或 BrdU 加（53）Sm-EDTMP 会显著降低 PCE 频率，从 32 小时持续到实验结束。BrdU 加（53）Sm-EDTMP 组的 PCE 频率在最后时间明显低于 BrdU 对照组，并且远低于仅用（53）Sm-EDTMP 处理的组，后者恢复到基础值。结果表明，BrdU 取代的 DNA 中诱导了致命损伤，不易修复，并且不能进行细胞分裂和形成微核。
