Lipoxygenase: a new pathway for 2-aminofluorene bioactivation.

Soybean lipoxygenase mediated co-oxidation of 2-aminofluorene (2-AF), a putative carcinogen and teratogen, was examined. 2-AF metabolism was followed spectrally as a decrease in absorbance at 286 nm. The enzymatic oxidation displayed a pH optimum at 9.5 with a Km of 0.27 mM and specific activity of 521.7 +/- 46.6 nmol/min per nmol of enzyme. The generation of electrophilic 2-AF intermediate(s) capable of covalent binding to macromolecules was also investigated radiometrically. Significant binding to protein and calf thymus DNA was observed, suggesting clearly bioactivation of 2-AF. Several classical lipoxygenase inhibitors caused a marked inhibition of 2-AF oxidation as well as covalent binding to protein and DNA. These results strongly suggest that lipoxygenase is capable of 2-AF metabolism and this may represent another pathway for bioactivation of arylamines.