RT Journal Article
SR Electronic
T1 Production of a dimer of 2-acetylaminofluorene during the sulfation of N-hydroxy-2-acetylaminofluorene in vitro.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 296
OP 300
VO 7
IS 5
A1 L S Andrews
A1 L R Pohl
A1 J A Hinson
A1 C L Fisk
A1 J R Gillette
YR 1979
UL http://dmd.aspetjournals.org/content/7/5/296.abstract
AB During the sulfation of N-hydroxy-2-acetylaminofluorene (NOH-2AAF) by rat liver 100,000 g supernatant fraction in vitro, an unidentified metabolite is produced which accounts for 22% of the N-OH-2AAF metabolized. This product has been characterized as the 2AAF dimer, 1-(N-2'-fluorenylacetamido-2-acetylaminofluorene) by comparing its TLC, HPLC, UV, and mass spectral properties with a synthetic standard which was prepared from the reaction of N-acetoxy-2-acetylaminofluorene (N-AcO-2AAF) with 2AAF. Increasing amounts of 2AAF added to the incubation mixture of N-OH-[acetyl-14C]2AAF and rat liver 100,000 g supernatant fraction decreased the irreversible binding of 14C to protein, and increased the formation of 2AAF dimer proportionately. This suggests that the 2AAF dimer is formed from the reaction of 2AAF and the electrophilic species produced from the sulfated N-OH-2AAF. In the presence of the 9,000 g fraction of rat liver, the dimer of 2AAF was aroximately 1/25 as active as 2AAF in producing mutations in the Salmonella mutagenesis test system.