Different responses to phenobarbital promotion in the development of gamma-glutamyltranspeptidase-positive foci in the liver of rats initiated with diethylnitrosamine, N-hydroxy-2-acetyl-aminofluorene and aflatoxin B1.
The promoting activities of phenobarbital (PB) on the development of gamma-glutamyl-transpeptidase-positive (gamma-GT+) foci in rat liver with three different initiating agents were compared in a short-term system (8 weeks). Male F344 rats were initiated by a single application of 200 mg/kg of diethylnitrosamine (DEN), 30 mg/kg of N-hydroxy-2-acetylaminofluorene (N-OH-AAF), 1.0 or 0.5 mg/kg of aflatoxin B1 (AFB1) or the vehicles alone. Two weeks after the initiation, animals were placed on a 0.05% PB diet for 6 weeks. Partial hepatectomy was performed at the end of the third week of the experiment. As a positive control, some animals were fed diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) after the initiation. The number and area of gamma-GT+ foci in the liver were quantified. All three initiators showed a summation effect with 3'-Me-DAB on the appearance of gamma-GT+ foci. Promotion by PB, however, was observed only in DEN-initiated rats and not in N-OH-AAF- or AFB1-initiated rats. It is apparent from the present experimental data that the promoting potential of PB on liver carcinogenesis depends on the initiating agent.
Shirai
T
T
Imaida
K
K
Ohshima
M
M
Fukushima
S
S
Lee
M S
MS
King
C M
CM
Ito
N
N
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D006881:Hydroxyacetylaminofluorene; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000032:analysis*
D000348:Aflatoxins; D002273:Carcinogens; D004052:Diethylnitrosamine; D006881:Hydroxyacetylaminofluorene; D016604:Aflatoxin B1; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital