Fujitani T, Tada Y, Yoneyama M
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Toxicology. 1993 Nov 12;84(1-3):171-83. doi: 10.1016/0300-483x(93)90115-9.
Male F344 rats were given 0, 0.6, 1.2 or 2.4% of piperonyl butoxide in the diet. At 1, 2, 4 or 12 weeks after the beginning of the experiment, liver and kidney weight and serum clinical parameters were determined and livers and kidneys were examined with light microscopy. From 1 or 2-12 weeks, distinct increase of liver weight, changes in serum clinical parameters for liver damage, oval cell proliferation, bile duct hyperplasia, single cell necrosis, enlarged and vacuolated hepatocytes, enlarged nuclei and anisonucleosis were seen in treated rats. From 4-12 weeks, cell infiltration, focal necrosis, multinucleated hepatocytes and prominent nucleoli of hepatocytes were seen in treated rats. At 12 weeks microgranulomas were seen in treated rats. Especially in rats of the 2.4% group at 12 weeks, severe enlargement of hepatocytes, severe enlargement of nuclei and multinucleated hepatocyte were seen, suggesting preneoplastic alteration. Relative kidney weights and serum urea nitrogen levels were increased in treated rats from 1 or 2-12 weeks and at 12 weeks, atrophy of proximal tubules, dilation of tubules, cell infiltration, fibrosis and accumulation of yellow-brown pigment in the proximal tubular cells were seen.
给雄性F344大鼠喂食含0%、0.6%、1.2%或2.4%胡椒基丁醚的饲料。在实验开始后的1、2、4或12周，测定肝脏和肾脏重量以及血清临床参数，并对肝脏和肾脏进行光学显微镜检查。在1或2至12周期间，在接受处理的大鼠中可见肝脏重量明显增加、肝脏损伤的血清临床参数变化、卵圆细胞增殖、胆管增生、单细胞坏死、肝细胞肿大和空泡化、细胞核增大以及核大小不均。在4至12周期间，在接受处理的大鼠中可见细胞浸润、局灶性坏死、多核肝细胞以及肝细胞明显的核仁。在12周时，在接受处理的大鼠中可见微肉芽肿。尤其是在12周时2.4%组的大鼠中，可见肝细胞严重肿大、细胞核严重增大以及多核肝细胞，提示癌前改变。在1或2至12周以及12周时，接受处理的大鼠的相对肾脏重量和血清尿素氮水平升高，并且在12周时，可见近端小管萎缩、小管扩张、细胞浸润、纤维化以及近端小管细胞中黄褐色色素的蓄积。
