Metabolism of the renal carcinogen FNT by peroxidases

Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide (FNT) is a renal carcinogen in the rat. The peroxidative activity of prostaglandin H synthase oxidizes FNT into a reactive intermediate which forms 5-(S)-substituted thioether conjugates with glutathione and N-acetylcysteine. These conjugates are also formed during horseradish peroxidase oxidation of FNT. The conjugate was identified by the combined results of comparative u.v./vis. spectrophotometry, chromatographically-assisted hydrodynamic voltammetry and proton n.m.r. spectroscopy. The relative rate of PHS metabolism of FNT was similar to that observed with benzidine and 5-fold faster than ANFT, its 5-nitrofuro-2-aminothiazole analogue. These results indicate that the pathogenic effects of FNT may be caused by its peroxidative activation and that cellular thiols may attenuate the toxic effects of FNT by conjugate formation.