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 hepatocarcinogeneis 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 μmol/kg), or both (150 μmol/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 com pounds 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 palmit ate 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.
|Number of pages||6|
|State||Published - Feb 1995|
Bibliographical noteFunding Information:
I. B. and L.-C. C. have contributed equally to the project and both should be considered as first authors. This study was supported by grants from NIH (CA 43719, CA 01688 and ES 07266) and NATO (CRG 890526), a Peace Fellowship from the Egyptian Embassy (I. B.), a Dissertation Year Fellowship from the Graduate School of the University of Kentucky (L.-C. C), and the University of Kentucky Agricultural Experiment Station. The authors would like to thank T. Lay, Dr V. Tatum and Dr T. Borges for technical assistance and Dr R. Kryscio for statistical analyses.
ASJC Scopus subject areas
- Cancer Research