van Rongen E, van der Kogel J, Durham S K
Radiobiological Institute TNO, Rijswijk, The Netherlands.
Int J Radiat Biol. 1989 Apr;55(4):661-77. doi: 10.1080/09553008914550701.
Cisplatin was administered as a single i.p. dose of 5 mg/kg to WAG/Rij rats at intervals of 7 days or 0.5 h before, or 7 days after graded X-ray doses to the left kidney. The right kidney was surgically removed 4 weeks after irradiation. Renal function was determined by measuring total urine volume excreted in 24 h, urine osmolality and serum urea. The severity of alterations in the various anatomic compartments of the kidney induced by the various treatments were graded histologically. The administration of 2 or 5 mg/kg cisplatin alone did not alter any of the kidney function parameters. Isoeffective radiation doses calculated for each of the functional parameters continuously decreased with increasing time after treatment. Differences between the isoeffective doses for the three combined treatments and for treatment with irradiation alone were only observed for urine osmolality and urine volume which primarily are tubular-related functional parameters. The histopathological grading studies also indicated that enhancement by cisplatin of radiation-induced damage was almost entirely confined to the tubules. The results of this study indicate that the sequence and length of time between treatments is an important variable in the development of cisplatin plus radiation-induced renal injury, but that none of the tested combinations showed a more than additive toxicity.
顺铂以5mg/kg的单次腹腔注射剂量给予WAG/Rij大鼠，给药时间间隔为7天，或在对左肾进行分级X射线照射前0.5小时，或照射后7天。照射后4周通过手术切除右肾。通过测量24小时内排出的总尿量、尿渗透压和血清尿素来测定肾功能。通过组织学对各种治疗引起的肾脏各个解剖区域的改变严重程度进行分级。单独给予2mg/kg或5mg/kg顺铂不会改变任何肾功能参数。随着治疗后时间的增加，为每个功能参数计算的等效辐射剂量持续降低。仅在尿渗透压和尿量（主要是与肾小管相关的功能参数）方面观察到三种联合治疗与单独放疗的等效剂量之间的差异。组织病理学分级研究还表明，顺铂对辐射诱导损伤的增强作用几乎完全局限于肾小管。本研究结果表明，治疗之间的顺序和时间长度是顺铂加辐射诱导肾损伤发生发展中的一个重要变量，但所测试的组合均未显示出超过相加的毒性。
