Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Environ Toxicol Pharmacol. 1999 Jul;7(3):179-87. doi: 10.1016/s1382-6689(99)00012-5.
A recent notion, that a variety of toxicants causing necrosis can lead to apoptosis as well, has been demonstrated with cultured cells, but not with in an vivo system. In the present study, we examined the induction of both apoptosis and necrosis in the kidneys of Wistar rats exposed to mercuric chloride (HgCl(2)). A single injection of HgCl(2) to rats at a dose of 4 mg/kg resulted in an increase in the renal DNA fragmentation evaluated as an occurrence of apoptosis, prior to urinary excretion of alkaline phosphatase (ALP) and renal morphological changes assessed as necrotic phenomena. The mercury-promoted DNA fragmentation was induced in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and morphological observation of the nuclei revealed that apoptotic cells caused by HgCl(2) were predominantly found in the proximal tubules, but not in the distal tubules, glomeruli or medullary tubules. When we confirmed the proximal tubular-selective apoptosis by inorganic mercury with a combined technique of TUNEL staining with synchrotron radiation X-ray fluorescence (SR-XRF) imaging, it was shown that the apoptotic cells localized in the proximal tubules did contain higher level of mercury. Thus these results indicate that the proximal tubular cells-dominant site-specific distribution of mercury appears to be associated with induction of renal apoptosis and necrosis.
最近的一种观点认为，多种引起坏死的毒物也可以导致细胞凋亡，这一观点在培养细胞中得到了证实，但在体内系统中尚未得到证实。在本研究中，我们研究了氯化汞（HgCl(2)）暴露的 Wistar 大鼠肾脏中细胞凋亡和坏死的诱导。大鼠单次注射 4mg/kg 的 HgCl(2)后，在碱性磷酸酶（ALP）尿液排泄和肾形态学变化（评估为坏死现象）之前，肾 DNA 片段化增加，评估为细胞凋亡的发生。汞促进的 DNA 片段化呈剂量依赖性诱导。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色和细胞核的形态观察表明，HgCl(2)引起的凋亡细胞主要存在于近端肾小管，而不是远端肾小管、肾小球或髓质小管。当我们通过 TUNEL 染色与同步辐射 X 射线荧光（SR-XRF）成像相结合的技术确认了无机汞引起的近端肾小管选择性凋亡时，结果表明，定位在近端肾小管中的凋亡细胞确实含有更高水平的汞。因此，这些结果表明，汞在近端肾小管中的优势局灶性分布似乎与肾细胞凋亡和坏死的诱导有关。
