Molecular Pharmacology, Vol 8, 645-650, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Effects of the Carcinogen 2-Acetylaminofluorene and Its Derivatives on Bacteria and Bacteriophages

¹ Fels Research Institute, Department of Biochemistry, and Department of Microbiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

The interaction of various carcinogenic fluorene derivatives with genomes was studied by examining the viability of bacteria and phage and the induction of prophage. Two strains of Salmonella typhimurium, wild type (hcr⁺) and an ultraviolet-sensitive mutant (hcr^-) lysogenic for phage P221, were used for cell viability and prophage induction studies. Free T5 phage particles were employed for phage viability studies; T5 phage was assayed on Escherichia coli K-12.

Incubation with 1 mM 2-nitro-, 2-amino-, 2-diacetylamino-, 2-acetylamino-, or N-hydroxy-2-acetylaminofluorene or its glucuronide (sodium salt) for 1 hr caused neither changes in bacterial viability nor prophage induction.

N-Hydroxy-2-aminofluorene was very effective in induction of prophage and causing loss of bacterial cell viability. Loss of viability of hcr^- cells was more rapid than that of wild type (hcr⁺) cells with this compound when tested at 0.1 and 0.2 mM levels. This compound at 0.1 mM also caused rapid prophage induction in hcr^- cells compared to wild type cells. These results suggest that N-hydroxy-2-aminofluorene damages the bacterial genome, which is restored by the bacterial repair mechanism. Similarly, nitrosofluorene (0.5 mM) and N-acetoxy-2-acetylaminofluorene (1 mM) also caused prophage induction and loss of bacterial cell viability. However, these compounds were not as effective as N-hydroxy-2-aminofluorene. In the presence of either rat liver cytosol fraction or guinea pig liver microsomes, N-hydroxy-2-acetylaminofluorene effectively induced the prophage and caused loss of hcr^- cell viability.

Among the compounds tested at 1 mM levels, only N-hydroxy-2-aminofluorene and N-acetoxy-2-acet-acetylaminofluorene caused significant loss of viability of free T5 phage particles, the latter being twice as effective as the former.

These data demonstrate a correlation between the carcinogenicity of fluorene compounds and their effects on bacteria and bacteriophages. Such systems might serve as useful tools in testing for active and ultimate carcinogens.