Nakazawa Tomomi, Yamaguchi Yuko, Fukunaga Yachiyo, Tamura Kazutoshi
Pathology Division, Tsukuba Research Institute, Bozo Research Center Inc., 8 Okubo, Tsukuba-shi, Ibaraki 300-2611, Japan.
Pathology Division, Gotemba Research Institute, Bozo Research Center Inc., 1284 Kamado, Gotemba, Shizuoka 412-0039, Japan.
J Toxicol Pathol. 2022 Jan;35(1):123-127. doi: 10.1293/tox.2021-0010. Epub 2021 Sep 24.
In accordance with a previous report on cystic kidneys induced in rat neonates when dosed with p-cumylphenol (PCP) for 18 days from postnatal day (PND) 4, 3 rat neonates were dosed with PCP once a day for 14 days, either from PND 14, 21, 28, 35, or 42 as W2, W3, W4, W5, and W6 groups, respectively, to investigate whether dosing periods in different PNDs influenced the development of cystic renal tubules. The lesion was striking in the W2 group and at a lesser magnitude in the W3 group, whereas either kidney was unaffected when dosing was initiated beyond PND 28. These findings, together with the results from the previous study, suggested that PND 14-28 is a critical dosing period for PCP to develop cystic kidneys in rat neonates. The lining epithelium of the cystic tubules was immunohistochemically positive for AQP2. This finding and the anatomical location indicated that the cystic tubules were of collecting duct origin. Either obstruction, fluid accumulation, or reparative hyperplasia of the lining epithelium was unlikely to be involved in the formation of cystic tubules lined with a monolayer of cuboidal or columnar epithelium with a high nuclear density. Thus, the follow-up investigation on PCP suggested a critical dosing period of PND 14-28 in rat neonates for the development of cystic dilation of renal collecting ducts. This study further supports that additive hyperplasia of the lining epithelium is a fundamental basis of this unique lesion.
根据之前的一份报告，从出生后第4天起给新生大鼠连续18天喂食对异丙基苯酚（PCP）会导致其出现多囊肾。将3只新生大鼠分别从出生后第14天、21天、28天、35天或42天开始，每天喂食一次PCP，持续14天，分别作为W2、W3、W4、W5和W6组，以研究在不同出生后天数给药是否会影响肾囊肿的形成。结果发现，W2组的病变最为明显，W3组次之，而在出生后第28天之后开始给药时，双侧肾脏均未受影响。这些发现与之前的研究结果共同表明，出生后第14 - 28天是PCP诱导新生大鼠形成多囊肾的关键给药期。肾囊肿的内衬上皮细胞免疫组化检测显示水通道蛋白2（AQP2）呈阳性。这一发现及解剖位置表明，肾囊肿起源于集合管。由单层立方或柱状上皮细胞内衬、细胞核密度较高的肾囊肿形成不太可能涉及管腔阻塞、液体蓄积或内衬上皮的修复性增生。因此，对PCP的后续研究表明，出生后第14 - 28天是新生大鼠肾集合管发生囊性扩张的关键给药期。本研究进一步支持内衬上皮细胞的增生是这一独特病变的基本基础。
