Reddy J K, Rao M S
Br J Cancer. 1978 Oct;38(4):537-43. doi: 10.1038/bjc.1978.241.
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.
二乙基亚硝胺（DEN），以100份/10⁶的浓度添加到饮用水中，持续14天，在喂食对照饮食的18只雄性F344大鼠中，有5只（27%）在48周时出现了极少数肝脏肿瘤。当DEN处理一周后，接着以0.1%的日粮水平持续喂食降血脂肝过氧化物酶体增殖剂Wy-14,643时，所有28只大鼠（100%）在38至48周之间出现了数量显著更多的肝脏肿瘤。此外，在22周时进行的剖腹手术显示，在开始给予DEN后喂食Wy-14,643的几只大鼠出现了可见的肝脏结节，这表明Wy-14,643也加速了这些肿瘤的出现。在开始给予DEN后，以0.5%的日粮水平给予另一种过氧化物酶体增殖剂氯贝丁酯，也导致肝脏肿瘤发生显著增强。然而，氯贝丁酯对肝脏肿瘤发展的增强作用小于Wy-14,643。Wy-14,643的显著增强作用可能归因于其显著的肝肿大和过氧化物酶体增殖特性。
