Metabolism of the carcinogenic air pollutant 2-nitrofluorene in the rat.

After a single oral dose of 2-nitro [9-14C]fluorene to rats, radioactivity with associated mutagenic activity was rapidly excreted in both urine and faeces, urine being the major excretory route. The major part of the urinary mutagenicity was associated with the unconjugated fraction of metabolites which consisted of a range of hydroxylated acetylaminofluorenes in addition to a number of hydroxylated nitrofluorenes. The formation of hydroxylated acetylaminofluorenes supports the contention that 2-nitrofluorene, in vivo, enters the metabolic pathway of the well-known carcinogen 2-acetylaminofluorene. The single most mutagenic metabolite of 2-nitrofluorene was a hydroxylated nitrofluorene; the formation of this metabolite was markedly increased when the rats had been treated with beta-naphthoflavone. Finally, an alternative pathway is discussed for the formation of 1- and 3-hydroxyacetylaminofluorenes.