The effects of partial hepatectomy and of promoters on macromolecular binding of trans-4-acetylaminostilbene metabolites in liver and some extrahepatic tissues of rats.

Trans-4-acetylaminostilbene (trans-AAS) is a complete carcinogen for sebaceous glands and an initiator for liver in rats. Partial hepatectomy alone or in combination with phenobarbital, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane or diethylstilbestrol produce liver tumors in trans-AAS pretreated rats. The effects of such secondary treatments on the macromolecular binding of [3H]trans-AAS metabolites was studied in several tissues. Partial hepatectomy was performed either 24 h before or after a single trans-AAS dose, and binding to proteins, RNA and DNA was measured 1, 3, and 17 d after the last treatment. Initial DNA-binding in liver was, if at all, somewhat lower than in controls, and then decreased more rapidly independent of the time of partial hepatectomy. In extrahepatic tissues, exposure and initial macromolecular binding was considerably higher, and elimination differentially delayed, if partial hepatectomy preceded dosing. With subsequent partial hepatectomy, initial binding was similar to controls, but elimination of DNA-binding was retarded in lung and glandular stomach. In a similar experiment, promoters were added to the feed 1 d after a single trans-AAS dose and macromolecular binding was determined 2 and 16 d thereafter. DNA-binding was little affected in liver, and in extrahepatic tissues at the first time point. In lung and glandular stomach its elimination was retarded, while in kidney DNA-binding even increased during promoter feeding. It is concluded that the secondary treatments have little impact on the primary lesion in the target tissue liver, but profoundly alter the disposal of trans-AAS metabolites which leads to increased tissue doses in extra-hepatic tissues.