Vitamin E modulation of hepatic focal lesion growth in mice.
The effect of DL-alpha-tocopherol acetate (vitamin E) on 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 dose groups: 0 mg vitamin E/kg NIH-07 diet, 50 mg vitamin E/kg NIH-07 diet (control diet), 250 mg vitamin E/kg NIH-07 diet, and 450 mg vitamin E/kg NIH-07 diet. Mice were euthanized after either 30 or 60 days of dietary treatment. In normal (nonlesion) liver, vitamin E deficiency (0 mg/kg diet) increased hepatic DNA synthesis. In addition, vitamin E supplementation (450 mg/kg diet) decreased the incidence of hepatic apoptosis, while vitamin E deficiency (0 mg/kg diet) increased the incidence of hepatic apoptosis. The effect of vitamin E-induced lesion growth was examined by measuring the number of focal lesions per liver and the relative focal lesion volume. High-dose vitamin E supplementation (450 mg/kg diet) appeared to enhance the growth of hepatic focal lesions. In particular, basophilic lesions appeared to be the most sensitive to high-dose vitamin E modulation (450 mg/kg diet) as evidenced by increased number, volume, and labeling index of hepatic focal lesions. Vitamin E deficiency also appeared to enhance the growth of hepatic focal lesions, though to a lesser extent than vitamin E supplementation (450 mg/kg diet). In the present study, both vitamin E supplementation (450 mg/kg diet) and deficiency (0 mg/kg diet) appeared to enhance focal lesion growth albeit neither treatment enhanced lesion growth as dramatically as known nongenotoxic hepatocarcinogens (e.g., phenobarbital and dieldrin). The data presented here suggest that oxidative stress in focal hepatocytes may be a component of the liver tumor promotion process.
Kolaja
K L
KL
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202, USA.
Klaunig
J E
JE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D014810:Vitamin E / Q000008:administration & dosage*; D014811:Vitamin E Deficiency / Q000378:metabolism
D002273:Carcinogens; D004273:DNA, Neoplasm; D014810:Vitamin E; D004052:Diethylnitrosamine; D001973:Bromodeoxyuridine