Biochemical effects of two promoters of hepatocarcinogenesis in rats.
The effects of two promoters of hepatocarcinogenesis--phenobarbital and butylated hydroxytoluene (BHT)--on five hepatic biochemical parameters were examined in adult female rats. Phenobarbital given orally in two doses each of 110 mg/kg 21 and 4 hr before the rats were killed caused large increases in hepatic ornithine decarboxylase (ODC) activity and cytochrome P-450 content. Extending the number of phenobarbital treatments to five increased the hepatic enzyme induction and also caused a minor decrease in hepatic glutathione and a small increase in serum alanine aminotransferase activity. Two oral doses of 700 mg BHT/kg (20% of the LD50) caused hepatic DNA damage and induction of both ODC activity and cytochrome P-450 content. When the dose of BHT was reduced from 700 to 140 mg/kg no significant effects on the biochemical parameters were found. Both promoters of hepatocarcinogenesis were identified by their induction of ODC, a marker for promotional potential, but only BHT showed a potential for carcinogenic initiation. The biochemical parameters examined, particularly the alkaline elution technique for DNA damage, ornithine decarboxylase activity and serum alanine aminotransferase, may constitute a useful assay system for examining a compound's potential for carcinogenic initiation, carcinogenic promotion and cellular toxicity.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D002084:Butylated Hydroxytoluene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D009955:Ornithine Decarboxylase; D005978:Glutathione; D010634:Phenobarbital