Berberian I, Chen L C, Robinson F R, Glauert H P, Chow C K, Robertson L W
Graduate Center for Toxicology, University of Kentucky, Lexington 40506.
Carcinogenesis. 1995 Feb;16(2):393-8. doi: 10.1093/carcin/16.2.393.
The purpose of this study was to determine the effects of dietary vitamin A on the tumor promoting effect of 3,3',4,4'-TCB and 2,2',4,4',5,5'-HCB in a two-stage rat hepatocarcinogenesis model with diethylnitrosamine (DEN, 150 mg/kg) as the initiator. Two weeks after DEN injection rats were fed a purified diet containing either 2000 or 100,000 IU of vitamin A in the form of retinyl palmitate. Rats received four biweekly injections of 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB (300 mumol/kg), or both (150 mumol/kg each) in corn oil (10 ml/kg) for 8 weeks. Control animals received vehicle only. Six rats in each group that received no DEN treatment were used as additional control animals. Ten days after the last injection the rats were killed. In rats fed the low retinyl palmitate diet, treatment with 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB or both compounds lowered hepatic retinyl palmitate content. This effect was prevented by high dietary retinyl palmitate supplementation in rats treated with 2,2',4,4',5,5'-HCB, but not 3,3',4,4'-TCB or both compounds together. Histopathological examination of the liver showed that high dietary retinyl palmitate lessened the severity of hepatocellular necrosis and fatty changes induced by 3,3',4,4'-TCB alone or in combination with 2,2',4,4',5,5'-HCB. The latter did not cause significant pathological lesions to the liver. However, high dietary retinyl palmitate was not able to prevent thymic involution caused by 3,3',4,4'-TCB. The number and volume of altered hepatic foci were increased by 2,2',4,4',5,5'-HCB and particularly 3,3',4,4'-TCB; no synergistic effect was seen. Supplementation with high dietary retinyl palmitate diminished the number and volume of foci. These results show that supplementation with high dietary retinyl palmitate protects against hepatocellular necrosis, fatty changes, and preneoplastic changes induced by 3,3',4,4'-TCB as well as against preneoplastic changes induced by 2,2',4,4',5,5'-HCB. In addition, these two agents did not synergistically induce preneoplastic changes in DEN-induced rats.
本研究的目的是在以二乙基亚硝胺（DEN，150 mg/kg）为启动剂的两阶段大鼠肝癌发生模型中，确定膳食维生素A对3,3',4,4'-四氯联苯（3,3',4,4'-TCB）和2,2',4,4',5,5'-六氯联苯（2,2',4,4',5,5'-HCB）促癌作用的影响。在注射DEN两周后，给大鼠喂食含有2000或100,000 IU棕榈酸视黄酯形式维生素A的纯化日粮。大鼠每两周接受4次3,3',4,4'-TCB、2,2',4,4',5,5'-HCB（300 μmol/kg）或两者（各150 μmol/kg）在玉米油（10 ml/kg）中的注射，持续8周。对照动物仅接受溶剂。每组中6只未接受DEN处理的大鼠用作额外的对照动物。最后一次注射10天后处死大鼠。在喂食低棕榈酸视黄酯日粮的大鼠中，用3,3',,4,4'-TCB、2,2',4,4',5,5'-HCB或两种化合物处理均降低了肝脏棕榈酸视黄酯含量。在用2,2',4,4',5,5'-HCB处理的大鼠中，高膳食棕榈酸视黄酯补充可预防这种作用，但对3,3',4,4'-TCB或两种化合物联合处理则无效。肝脏组织病理学检查表明，高膳食棕榈酸视黄酯减轻了单独使用3,3',4,4'-TCB或与2,2',4,4',5,5'-HCB联合使用所诱导的肝细胞坏死和脂肪变性的严重程度。后者未对肝脏造成明显的病理损害。然而，高膳食棕榈酸视黄酯无法预防3,3',4,4'-TCB引起的胸腺萎缩。2,2',4,4',5,5'-HCB特别是3,3',4,4'-TCB增加了肝脏病变灶的数量和体积；未观察到协同作用。高膳食棕榈酸视黄酯补充减少了病灶数量和体积。这些结果表明，高膳食棕榈酸视黄酯补充可预防3,3',4,4'-TCB诱导的肝细胞坏死、脂肪变性和癌前病变以及2,2',4,4',5,5'-HCB诱导的癌前病变。此外，这两种药剂在DEN诱导的大鼠中未协同诱导癌前病变。
