Enhancement of GST-P positive liver cell foci development by a medium-term carcinogenicity bioassay using repeated administration of D-galactosamine.
This study was performed for developing a new medium-term carcinogenicity bioassay treated with D-galactosamine (DGA) as a non-surgical method without partial hepatectomy (PH). In male F344 rats initiated with diethylnitrosamine (DEN, 200 mg/kg i.p.), enhancing effects of DGA (300 mg/kg i.p.) given twice 3 weeks apart during the promotion procedure with 2-acetylaminofluorene (2-AAF, 0.01% in diet) were compared along with those of PH by analyzing preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatocyte foci as endpoint marker lesions. The DGA treatment did not affect the body weight gain whereas the PH treatment caused a transient body weight loss. Although both bioassay protocols were effective to detect the potential hepatocarcinogenicity of 2-AAF, the number and area of GST-P positive foci per cm2 were larger in the bioassay using DGA than in that using PH, the number being statistically significant (P < 0.05). Our results thus suggest 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 carcinogens.
Kim
H C
HC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Yusongku, Daejon, South Korea.
Lee
Y S
YS
Furukawa
F
F
Nishikawa
A
A
Takahashi
M
M
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001681:Biological Assay / Q000379:methods; D015197:Carcinogenicity Tests / Q000379:methods*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004052:Diethylnitrosamine; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005688:Galactosamine / Q000008:administration & dosage / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006498:Hepatectomy; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D010920:Placenta / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
D002274:Carcinogens, Environmental; D004052:Diethylnitrosamine; D005688:Galactosamine; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase