Oxidative activation of benzidine and its derivatives by peroxidases

Area of Science:

• Toxicology
• Carcinogenesis
• Biochemistry

Background:

• Benzidine (4,4'-diaminobiphenyl) is a known human carcinogen.
• Occupational exposure in the dye industry led to bladder cancer epidemics.
• Oxidation of benzidine produces a detectable radical cation.

Purpose of the Study:

• To describe the structures of novel benzidine metabolites.
• To investigate the binding of benzidine to protein and nucleic acid via peroxidases.
• To explore the relevance of these metabolic processes to in vivo benzidine carcinogenesis.

Main Methods:

• Electron spin resonance to detect the benzidine radical cation.
• Peroxidase-catalyzed oxidation of benzidine.
• Characterization of adducts formed with phenol and thiol compounds.

Main Results:

• Novel metabolites formed from benzidine oxidation with phenol and thiol compounds were structurally characterized.
• Peroxidases, including prostaglandin synthase, were shown to catalyze benzidine binding to protein and nucleic acid.
• The exact nature of these protein and nucleic acid adducts remains unknown.

Conclusions:

• Benzidine undergoes oxidative metabolism generating reactive electrophiles.
• These electrophiles form adducts with various compounds, including biomolecules.
• Ongoing research debates whether benzidine activation occurs in target tissues or post-hepatic metabolism.