Modifying potential of thirty-one chemicals on the short-term development of gamma-glutamyl transpeptidase-positive foci in diethylnitrosamine-initiated rat liver.

The modifying potential of 31 different compounds on the development of gamma-glutamyl transpeptidase-positive (gamma-GT+) liver cell lesions was compared in an in vivo short-term assay system. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to partial hepatectomy at week 3. Modifying potential was scored by comparing the number and area (mm2)/cm2 of induced gamma-GT+ foci with those of the corresponding control group given DEN alone. 2-Acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, phenobarbital, barbital, dipyrone and deoxycholic acid caused a significant enhancement of both the number and area of foci. 4-Acetylaminofluorene, ethionine, benzo[alpha]pyrene, disulfiram and cholic acid had a moderate enhancing effect, whereas slight, but not unequivocal, increases in gamma-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. In contrast, acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, and ethyl alcohol showed clear inhibitory effects. It is concluded that the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.