Effect of dietary retinyl palmitate on the promotion of altered hepatic foci by 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl in rats initiated with diethylnitrosamine.
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.
Graduate Center for Toxicology, University of Kentucky, Lexington 40506.
I
I
Berberian
L C
LC
Chen
F R
FR
Robinson
H P
HP
Glauert
C K
CK
Chow
L W
LW
Robertson
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000633:toxicity*; D004224:Diterpenes; D004347:Drug Interactions; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008748:Methylcholanthrene / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D004052:Diethylnitrosamine; D008748:Methylcholanthrene; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl