Vitamin E modulation of dieldrin-induced hepatic focal lesion growth in mice.
The effect of vitamin E on dieldrin-induced hepatic focal lesion growth in male B6C3F1 mice previously treated with diethylnitrosamine (DEN) was investigated. After hepatic focal lesions were formed, mice were placed into one of the following treatment groups: Group 1, 50 mg vitamin E/kg diet (control NIH-07 diet); Group 2, 10 mg dieldrin/kg NIH-07 diet; Group 3, 10 mg dieldrin and 450 mg vitamin E/kg NIH-07 diet; and Group 4, 450 mg vitamin E/kg NIH-07 diet. Mice were killed and necropsied after 30 and 60 d of dietary treatment. The effect of treatment on lesion growth was examined by measuring the number of focal lesions per liver and the relative hepatic focal lesion volume. In addition, the possible cellular mechanism of focal hepatocyte growth was investigated by examining both focal DNA synthesis and apoptosis. Dieldrin treatment alone (Group 2) increased the focal lesion volume, focal lesion number, and focal lesion labeling index. Supplementation with vitamin E (Group 3) blocked this effect. Vitamin E supplementation to the diet alone (Group 4) also enhanced focal lesion growth and increased the number of lesions per liver, the relative focal volume, and the labeling index in hepatic focal lesions. Interestingly, vitamin E supplementation inhibited apoptosis in normal liver but did not produce an observable decrease in apoptosis in hepatic focal lesions. The present study showed that dieldrin (Group 2) or vitamin E supplementation alone (Group 4) promoted the growth of hepatic focal lesions in mice. However, when vitamin E is supplemented to dieldrin-fed mice (Group 3), there is an inhibition of hepatic focal lesion growth.
Kolaja
K L
KL
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202, USA.
Xu
Y
Y
Walborg
E F
EF
Stevenson
D E
DE
Klaunig
J E
JE
D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004026:Dieldrin / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D014810:Vitamin E / Q000627:therapeutic use*
D002273:Carcinogens; D007306:Insecticides; D014810:Vitamin E; D004026:Dieldrin