The biological activity of single-stranded phi X174 DNA, modified by N-hydroxy-2-aminofluorene, is inhibited by guanine imidazole ring-opening of the major, non-lethal aminofluorene-DNA adduct.
The major aminofluorene-DNA derivative, found in the liver of rats after administration of the hepatocarcinogen N-acetyl-2-aminofluorene and identified as N-(deoxyguanosin-8-yl)-2-aminofluorene (dGuo-C8-AF), was introduced in different amounts in single-stranded phi X174 DNA by reacting the DNA with tritium labeled N-hydroxy-2-aminofluorene. The modified DNA was subsequently incubated in 0.1 M NaOH at 37 degrees C for increasing periods of time to convert the dGuo-C8-AF residues into their guanine imidazole ring-opened forms. The degree of conversion was determined by measuring the amount of residual N-(guanin-8-yl)-2-aminofluorene in trifluoroacetic acid hydrolyzates of the alkali-treated DNA by h.p.l.c. In addition, the effect of ring opening on the biological activity of the DNA was monitored by transfecting the DNA to Escherichia coli wild-type spheroplasts. The results indicate that the major aminofluorene-DNA adduct formed initially, which contributes little to inactivation, becomes lethal when its guanine imidazole ring is opened.
D010584:Bacteriophage phi X 174 / Q000235:genetics*; D004279:DNA, Viral / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism* / Q000633:toxicity; D009690:Nucleic Acid Conformation
D004279:DNA, Viral; D005449:Fluorenes; C031838:N-(deoxyguanosin-8-yl)-2-aminofluorene; C001368:N-hydroxy-2-aminofluorene; D003849:Deoxyguanosine