Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
J Cancer Res Clin Oncol. 1993;119(8):463-9. doi: 10.1007/BF01215926.
Accumulation of alpha 2u-globulin and induction of cell proliferation were examined in kidneys of rats exposed to KBrO3, KBr or NaBrO3 in their drinking water. Hyaline droplets observed after KBrO3 or NaBrO3 administration to male rats were specifically immunostained for alpha 2u-globulin. Increases in cell proliferation were found in the proximal tubules of male rats given KBrO3 or NaBrO3 but not KBr for 2, 4, and 8 weeks. No such change was evident in KBrO3-treated female rats or the distal tubules of any treated animal. The concordance between hyaline droplet accumulation and increased cell turnover suggests that KBrO3- and NaBrO3-induced cell replication in kidneys of male rats may result from alpha 2u-globulin nephropathy. Considering the fact that KBrO3 has genotoxic potential involving oxidative stress, we hypothesize that the induced cell proliferation might predominantly play an additive role in its carcinogenesis. Furthermore, the present data, showing similar effects of NaBrO3 on the rat kidney, are of direct significance to its risk assessment.
研究了饮用含溴酸钾(KBrO3)、溴化钾(KBr)或溴酸钠(NaBrO3)的水的大鼠肾脏中α2u球蛋白的蓄积情况以及细胞增殖的诱导情况。对雄性大鼠给予KBrO3或NaBrO3后观察到的透明滴进行了α2u球蛋白特异性免疫染色。给予KBrO3或NaBrO3而非KBr的雄性大鼠在2周、4周和8周时,近端小管出现细胞增殖增加。在接受KBrO3处理的雌性大鼠或任何处理动物的远端小管中未观察到明显变化。透明滴蓄积与细胞更新增加之间的一致性表明,KBrO3和NaBrO3诱导的雄性大鼠肾脏细胞复制可能是由α2u球蛋白肾病引起的。鉴于KBrO3具有涉及氧化应激的遗传毒性潜力,我们推测诱导的细胞增殖可能在其致癌过程中主要起累加作用。此外,目前的数据表明NaBrO3对大鼠肾脏有类似影响,这对其风险评估具有直接意义。