The relationship of 2-acetamidofluorene mutagenicity in plate tests with its in vivo liver cell component distribution and its carcinogenic potential

1. Using a plating technique, the mutagenic potentials of 2-acetamidofluorence (AAF) and N-hydroxy-AAF were examined after metabolic activation by liver preparations from different animals. Animals used were: male and female rats; male rats treated with 3-methylcholanthrene (MC); male rats treated with AAF; hamsters; guinea pigs; cotton rats and baboons. Irrespective of the animal susceptibility to AAF carcinogenesis, mutation frequency was always increased in the Salmonella typhimurium TA 1538 tester strain. Indeed, the greater response was found in the presence of liver from cotton rats, a species which is resistant to AAF-induced carcinogenesis.

2. Carcinogen binding, with labelled molecules, was also studied in liver cell constituents of rats, guinea pigs and cotton rats. A much better correlation was found between carcinogenicity and carcinogen binding, at least in those species studied, than between carcogenicity and plate test mutagenicity. The difficulty which this new information poses for the interpretation of plate tests is discussed.

Abbreviations: AAF, 2-acetamidofluorence; EGTA, Ethyleneglycol-bis (β-aminoethyl ether) N,N′-tetra-acetic acid; MC, 3-methylcholanthrene