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.
Roy
S K
SK
Dept. of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa 33612.
Kulkarni
A P
AP
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005449:Fluorenes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013025:Glycine max / Q000201:enzymology; D013056:Spectrophotometry, Ultraviolet
D002273:Carcinogens; D005449:Fluorenes; D016859:Lipoxygenase Inhibitors; D012710:Serum Albumin, Bovine; C012177:2-aminofluorene; D009637:Masoprocol; D004247:DNA; D008084:Lipoxygenase