Demonstration of Initiation Potential of Carcinogens by Induction of Preneoplastic Glutathione S‐Transferase P‐Form‐positive Liver Cell Foci: Possible in vivo Assay System for Environmental Carcinogens

In a development trial for an initiation bioassay system, 7 known carcinogens and 1 suspected carcinogen were examined. In experiment 1, group 1 animals were initially subjected to partial hepatectomy (PH) 12 h before administration of diethylnitrosamine, 2‐amino‐3‐methylimidazo[4,5‐F]‐quinoline (IQ), captafol, α‐hexachlorocyclohexane or diethylstilbestrol (DES), then 2 weeks later underwent a promotion procedure comprising administration of phenobarbital (0.05% in diet) for 8 weeks and D‐galactosamine (300 mg/kg, i.g.) at week 3. Group 2 received the promotion protocol alone as in group 1. Initiating potential was assayed on the basis of significant increase in values of preneoplastic placental form glutathione S‐transferase‐positive (GST‐P(+)) foci of more than 3 cells in cross section at week 10. Numbers and areas of GST‐P(+) foci in group 1 given IQ, captafol and DES were significantly increased as compared to group 2, confirming the validity of the protocol as an initiation assay. In Experiment 2, group 1 rats were subjected to PH and 12 h later received a suspected carcinogenic mixture of opium pyrolysate (OP) or carcinogenic pesticide p, p′‐dichlorodiphenyltrichloroethane or hexachlorobenzene. Application of a modified promotion procedure comprising cholic acid (0.15%) and carbon tetrachloride (1 ml/kg, i.g.) revealed significant initiation potential for OP. Overall the results indicate that the current protocols may be useful for detection of the initiation potential of carcinogens irrespective of their mutagenicity.