Enhancement by Wy-14,643, a hepatic peroxisome proliferator, of diethylnitrosamine-initiated hepatic tumorigenesis in the rat.
Enhancement by Wy-14,643, a hepatic peroxisome proliferator, of diethylnitrosamine-initiated hepatic tumorigenesis in the rat.
复制标题
Wy-14,643（一种肝过氧化物酶体增殖剂）增强二乙基亚硝胺引发的大鼠肝肿瘤发生。
作者：
J. Reddy;M. Rao
饮用水中浓度为100份/10(6)的二乙基亚硝胺（DEN）持续14天，在48周后，18只（27%）雄性F=344只大鼠中有5只出现了很少的肝脏肿瘤。在DEN治疗一周后，以0.1%的膳食水平持续喂养低脂性肝过氧化物酶体增殖剂wy - 14643，所有28只大鼠（100%）在38至48周之间出现了显著增多的肝脏肿瘤。此外，22周剖腹手术显示，DEN启动后喂食wy - 14643的几只大鼠出现了可见的肝结节，这表明wy - 14643也加速了这些肿瘤的出现。DEN开始后，在饮食中添加0.5%的另一种过氧化物酶体增殖剂clofibrate，也会导致肝脏肿瘤发生的显著增强。然而，clofibrate对肝脏肿瘤发展的促进作用小于wy - 14643。wy - 14643的显著增强作用可能是由于其具有广泛的肝细胞增殖和过氧化物酶体增殖特性。
Diethylnitrosamine (DEN), at a concentration of 100 parts/10(6) in drinking water for 14 days, caused the development, by 48 weeks, of very few liver tumours in 5 of 18 (27%) male F=344 rats fed control diet. When the DEN treatment was followed one week later by continuous feeding of the hypolipidemic hepatic peroxisome proliferator, Wy-14,643, at 0.1% dietary level, all of 28 rats (100%) developed, between 38 and 48 weeks, a significantly higher number of liver tumours. Furthermore, laparotomy at 22 weeks revealed that several rats fed Wy-14,643 after DEN initiation had developed visible liver nodules, suggesting that Wy-14,643 also accelerates the appearance of these tumours. Administration of another peroxisome proliferator, clofibrate, at 0.5% level in the diet after DEN initiation, also caused a substantial enhancement of liver tumorigenesis. The enhancement of liver-tumour development by clofibrate, however, was less than that by Wy-14,643. The marked enhancing effect of Wy-14,643 may be due to its profound hepatomegalic and peroxisome proliferative properties.