4-Aminobiphenyl and Metabolism process in humans

4-Aminobiphenyl is an organic compound with the chemical formula C6H5C6H4NH2.It is an amine derivative of biphenyl.It is a colorless solid, but aged samples may appear colored.4-Aminobiphenyl used to be used as rubber antioxidant and dye intermediate.Exposure to this arylamine may occur through exposure to chemical dyes and inhalation of cigarette smoke.Studies have shown that 4-aminobiphenyl causes bladder cancer in humans and dogs by damaging DNA.Commercial production of 4-aminobiphenyl ceased in the United States in the 1950s due to its carcinogenic effects.

Synthesis and reactions 4-Aminobiphenyl

Like other aniline derivatives, 4-aminobiphenyl is weakly basic.It is prepared by reduction of 4-nitrobiphenyl, which is obtained together with 2-nitro derivatives by nitration of biphenyl. [9] Another reaction for the synthesis of 4-aminobiphenyl can be obtained using 4-azidobiphenyl.This can be accomplished by reacting 4-azidobiphenyl with phosphorus tetraiodide (P2I4), which cleaves nitrogen-nitrogen bonds. The reaction is done in benzene, then water is added to facilitate the formation of the amine.

Metabolism process in humans

Cytochrome P450 1A2 oxidizes 4-aminobiphenyl to N-hydroxy-4-aminobiphenyl.After O-acetylation, the latter can form DNA adducts.O-acetylation reactions are catalyzed by NAT, N-acetyltransferase; and UDP-glucuronosyltransferase (UGT).Two different enzymes can catalyze this reaction, NAT1 and NAT2.These enzymes also N-acetylate 4-aminobiphenyl.N-acetylated products are difficult to oxidize, so acetylation is considered as a detoxification step for aromatic amines.Glucuronidation is also a major metabolic pathway for carcinogenic aromatic amines.A certain human UGT catalyzes the formation of the N-glucuronide of 4-aminobiphenyl.Glucuronidation leads to inactivation and excretion, so N-glucuronidation also competes with N-oxidation.It is proposed that 4-aminobiphenyl induces bladder cancer through a mechanism involving hepatic N-oxidation and subsequent N-glucuronidation.N-hydroxyarylamine N-glucuronide conjugates are thought to be excreted from the liver and accumulate in the bladder lumen.4-Aminobiphenyl and the N-glucuronide of N-hydroxy-4-aminobiphenyl can be hydrolyzed by acidic urine to the corresponding arylamines, which in turn can enter the bladder epithelium and pass through peroxidation and/or O- Acetylation is further metabolized to form DNA adducts.