Enhancing effects of phenobarbital and 3-methylcholanthrene on GST-P-positive liver cell foci development in a new medium-term rat liver bioassay using D-galactosamine.
The carcinogenic potential of phenobarbital (PB) and 3-methylcholanthrene (3-MC) was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a nonsurgical method to induce liver cell regeneration in place of partial hepatectomy (PH). Rats were initially given a single ip injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 wk on basal diet received 2 ip injections of DGA (300 mg/kg) at the end of wk 2 and 5. They were treated with one of the test compounds PB or 3-MC in the diet or fed basal diet for wk 3-8 Carcinogenic potential was assessed by comparing the numbers and areas per square centimeter of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of test chemical-treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for PB, which is a nongenotoxic liver tumor promoter, and for 3-MC, which is a genotoxic nonliver carcinogen. Increases of liver/body weight ratios and serum total cholesterol were observed in rats treated with PB or 3-MC. Interestingly, interlobe differences were found on the development of GST-P+ liver cell foci. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive method to screen large-numbers of environmental liver and nonliver carcinogens.
Kim
H C
HC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Yusongku, Daejon, Korea.
Lee
Y S
YS
Nishikawa
A
A
D000818:Animals; D001681:Biological Assay; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity; D005688:Galactosamine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D004052:Diethylnitrosamine; D008748:Methylcholanthrene; D005688:Galactosamine; D005982:Glutathione Transferase; D010634:Phenobarbital