Promoting Effect of Aflatoxin B1 and D-Galactosamine on Development of Glutathione S-Transferase Positive Foci in Diethylnitrosamine-initiated Rat Liver

ABSTRACT

The enhancing potential of anatoxin a (AFB1) and D-galactosamine (DGA) on development of preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatic foci was examined using an in vivo mid-term assay system based on two-stage concept of hepatocarci-nogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) intraperi-toneally, and thereafter. with an interval of 2 weeks, AFBl at a graded concentration (0.06, 0.012, 0.0024, 0.00048, and 0.000096 mg/kg i.g.) and DGA (100 mg/kg i.p.) were administered for 6 weeks and then sacrificed. All rats were subjected to a two-thirds partial hepatectomy to induce a potent growth stimulus to DEN-altered hepatocytes at the week 3. The modifying potential was scored by comparing the number and the area (mm2) per cm2 of GST-P+ foci in the liver with those of the corresponding control group given DEN alone. AFBl (at a graded concentration between 96 ng/kg and 60 microgram/kg) exerted a strong promoting effect oil induction of GST-P+ foci with both the number and the area. The logarithmic dose of AFBl and the potency to promote hepatocarcinogenesis were in dose-dependent relationship. DGA, a known necrogenic chemical to cause periportal necrosis and stimulate hepatocellular proliferation. also revealed the increase in the area of GST-P+ foci. although its enhancing potentia1 was 1ess profound than that of AFBl. The results suggest that DGA is also a useful proliferative stimulus m improve the medium-termdetection of unknown carcinogens.