Hagiwara A, Sano M, Asakawa E, Tanaka H, Hasegawa R, Ito N
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1992 Sep;83(9):949-54. doi: 10.1111/j.1349-7006.1992.tb02006.x.
The modifying potential of two nephrotoxic agents, harman and norharman, on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatic carcinogenesis was investigated in male F344/DuCrj rats. Animals were given 0.1% EHEN in their drinking water for the first 2 weeks as an initiator. Subsequently, starting 3 weeks from the commencement, they were fed diet containing these compounds at concentrations of 1000, 500 or 0 ppm until week 26, and then killed for light microscopic examination. The mean numbers of renal tubular cell hyperplasias/cm2 and those of tumors/cm2 in rats given harman and norharman at 1000 ppm after initiation, but not at 500 ppm, were significantly increased as compared to the control values. However, neither compound modified liver carcinogenesis. It is concluded that harman and norharman show enhancing effects on rat kidney carcinogenesis, when ingested at dose levels which cause renal tubular damage.
在雄性F344/DuCrj大鼠中，研究了两种肾毒性物质哈尔满和去甲哈尔满对N-乙基-N-羟乙基亚硝胺（EHEN）诱导的肾和肝癌变的修饰作用。动物在最初2周饮用含0.1% EHEN的水作为启动剂。随后，从开始后的第3周起，给它们喂食含有浓度为1000、500或0 ppm这些化合物的饲料，直至第26周，然后处死进行光镜检查。启动后给予1000 ppm哈尔满和去甲哈尔满的大鼠，其每平方厘米肾小管细胞增生的平均数和每平方厘米肿瘤的平均数显著增加，而500 ppm组则未增加，与对照值相比有显著差异。然而，两种化合物均未改变肝癌变情况。结论是，当以导致肾小管损伤的剂量水平摄入时，哈尔满和去甲哈尔满对大鼠肾癌发生有增强作用。
