Host-mediated bacterial mutagenesis and enterohepatic circulation of benzidine-derived mutagenic metabolites in rodents.

Abstract

1. Administration of benzidine (100 mg/kg, i.p.) to bile duct-cannulated rats led to a sustained excretion of metabolites in bile which, following glucuronide hydrolysis, were mutagenic to Salmonella typhimurium strain TA98. 2. When the biliary metabolites were re-infused into the duodena of a further group of rats, enterohepatic circulation of mutagens was indicated by extensive re-excretion of biliary mutagens in the recipients. 3. Furthermore, in mouse host-mediated mutagenicity assays, both i.p. injection of benzidine (100 mg/kg) and intracaecal administration of rat biliary metabolites of benzidine produced a mutagenic response in Salmonella typhimurium strain TA98 cells isolated from the liver. 4. The results indicate that enterohepatic circulation adds to the biological persistence of reactive metabolites of benzidine and may contribute to the carcinogenicity of this aromatic amine.