A new medium-term bioassay system for detection of environmental carcinogens using diethylnitrosamine-initiated rat liver followed by D-galactosamine treatment and partial hepatectomy.

The effects of D-galactosamine on induction of preneoplastic glutathione S-transferase placental form positive liver foci were investigated in F344 rats pretreated with diethylnitrosamine (DEN) in an attempt to improve the predictive value of the medium-term bioassay system developed in our laboratory. Two weeks after the initial single ip dose (200 mg/kg) of DEN, administration of test compounds was commenced simultaneously with an ip injection of D-galactosamine at a dose of 300 mg/kg body wt. All rats were then subjected to two-thirds partial hepatectomy (PH) at week 5 and sacrificed for assessment of lesion yield at week 8. Measurement and comparison of the numbers and areas of glutathione S-transferase placental form positive (GST-P+) foci per cm2 revealed a positive response to more carcinogens, including non-hepatocarcinogens, than did the same bioassay system without injection of D-galactosamine. Thus the results suggest that inclusion of this extra proliferative stimulus may improve the medium-term detection of carcinogens and modifiers.