溴酸钾在离体大鼠肾近端小管和肾细胞核中诱导的氧化性DNA损伤。

Oxidative DNA damage induced by potassium bromate in isolated rat renal proximal tubules and renal nuclei.

作者信息

Sai K, Tyson C A, Thomas D W, Dabbs J E, Hasegawa R, Kurokawa Y

机构信息

Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.

出版信息

Cancer Lett. 1994 Nov 25;87(1):1-7. doi: 10.1016/0304-3835(94)90402-2.

DOI:10.1016/0304-3835(94)90402-2

PMID:7954362

Abstract

Oxidative damage caused by potassium bromate (KBrO3), a rat renal carcinogen, was investigated using in vitro preparations of rat renal proximal tubules (RPT) and renal nuclear fractions. Release of lactate dehydrogenase and decrease of SH-group content in RPT (1 mg protein/ml) by KBrO3 (0.5-5 mM) in a concentration- and time-dependent manner were observed. Peroxidized arachidonic acid and 8-hydroxydeoxyguanosine (8-OH-dG) levels in RPT were increased after administration of 2 and 5 mM KBrO3. 8-OH-dG formation was observed after incubation of renal nuclei with a lipid-peroxiding system, autooxidized methyl linolenate, or KBrO3. These findings provide support for involvement of lipid peroxidation in producing oxidized DNA damage by KBrO3 directly to RPT, the target site for renal carcinogenesis.

摘要

使用大鼠肾近端小管（RPT）和肾细胞核组分的体外制剂，研究了大鼠肾致癌物溴酸钾（KBrO₃）引起的氧化损伤。观察到KBrO₃（0.5 - 5 mM）以浓度和时间依赖性方式导致RPT（1 mg蛋白质/ml）中乳酸脱氢酶释放和SH基团含量降低。给予2 mM和5 mM KBrO₃后，RPT中过氧化花生四烯酸和8 - 羟基脱氧鸟苷（8 - OH - dG）水平升高。在用脂质过氧化系统、自动氧化的甲基亚麻酸酯或KBrO₃孵育肾细胞核后，观察到8 - OH - dG的形成。这些发现支持脂质过氧化参与KBrO₃直接对RPT（肾癌发生的靶位点）产生氧化DNA损伤的过程。