Otsuka M, Meistrich M L
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Radiat Res. 1990 Sep;123(3):285-91.
The time of appearance and the dose response of radiation effects in the mouse kidney were assessed from the determination of increases in labeling index, the appearance of proximal tubule cells with abnormally large nuclei, and kidney weight loss. Increased labeling indices and abnormally large nuclei were observed in the irradiated proximal tubule cells before any other histological changes were seen. The labeling index increased with dose (from 3 to 15 Gy) but not with time (from 1 to 12 months after irradiation). Increased labeling was evident as soon as 1 month after irradiation. Cell depletion as measured by a decrease in kidney weights compared to those of age-matched controls was not significant until 6 or more months after 11-, 13-, or 15-Gy irradiation. The frequency of cells with large nuclei increased steadily during the first 9 months after 15 Gy and tended to decline between 9 and 12 months, coincident with accelerating renal weight loss. These findings are consistent with the hypothesis that the production of these cells is a result of an abortive mitotic division and their loss is an eventual result of such an aberration. The increased proliferation induced by irradiation increases the chance for an abortive mitosis and death, presumably at a subsequent mitosis, of radiation-damaged proximal tubule cells, which is a major factor in the appearance of late radiation damage in the kidney.
通过测定标记指数的增加、出现细胞核异常增大的近端小管细胞以及肾脏重量减轻情况，评估小鼠肾脏中辐射效应的出现时间和剂量反应。在观察到任何其他组织学变化之前，在受辐照的近端小管细胞中就观察到标记指数增加和细胞核异常增大。标记指数随剂量（3至15 Gy）增加而增加，但不随时间（辐照后1至12个月）变化。辐照后1个月标记增加就很明显。与年龄匹配的对照组相比，通过肾脏重量减少来衡量的细胞耗竭在11、13或15 Gy辐照后6个月或更长时间才显著。15 Gy辐照后，细胞核大的细胞频率在前9个月稳步增加，在9至12个月之间趋于下降，这与肾脏重量加速减轻相一致。这些发现与以下假设一致，即这些细胞的产生是有丝分裂失败的结果，而它们的丢失是这种畸变的最终结果。辐照诱导的增殖增加增加了辐射损伤的近端小管细胞发生有丝分裂失败和死亡的机会，大概是在随后的有丝分裂时，这是肾脏晚期辐射损伤出现的一个主要因素。
