MODIFYING POTENTIAL OF 31 CHEMICALS ON THE SHORT-TERM DEVELOPMENT OF GAMMA-GLUTAMYL-TRANSFERASE TRANSPEPTIDASE-POSITIVE FOCI IN DIETHYLNITROSAMINE-INITIATED RAT-LIVER

  • 1 January 1984
    • journal article
    • research article
    • Vol. 75  (10) , 876-883
Abstract
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 [DEN] i.p. and 2 wk later were treated with test compounds for 6 wk and then sacrified, all rats being subjected to partial hepatectomy at wk 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 [a]pyrene, disulfiram and cholic acid had a moderate enhancing effect. Slight, but not unequivocal, increases in .gamma.-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. Acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene and ethyl alcohol showed clear inhibitory effects. Thus, the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.