Isolation and characterization of the major fluoranthene-hemoglobin adducts formed in vivo in the rat.

The binding of fluoranthene (FA) to hemoglobin was studied both in vitro and in vivo in the rat. The in vitro binding of microsomally activated FA to rat hemoglobin appeared to involve the fluoranthene 2,3-dihydrodiol-1,10b-epoxides. Three classes of hemoglobin adducts were observed in rats chronically administered FA in the diet. Based on high pressure liquid chromatography retention times, UV and mass spectral evidence, and behavior upon cis-diol affinity chromatography, the major class of globin adducts formed in vivo was demonstrated to result from binding of syn and anti isomers of FA 2,3-dihydrodiol-1,10b-epoxides to beta-cysteine-125 of rat hemoglobin. These adducts represented at least 41% of the total binding to globin. A minor class of adducts (12% of the total binding) appeared to involve the binding of an unidentified FA metabolite to the same cysteine residue of the protein. A substantial portion of FA binding to rat hemoglobin in vivo (29%) involved metabolic pathways which were not duplicated by simple in vitro systems. That portion of the binding to globin has not been characterized.