The formation of azoxy-2-phenylethane during the biological oxidation of phenylethylamine by rabbit liver microsomes

Incubation of phenylethylamine with rabbit liver microsomes,divalent manganese and a NADPH generating system leads to theformation of azoxy-2-phenylethane, among other metabolic products.Approximately 38 nmol of the azoxy compound is formed from 10µmol of phenylethylamine during a 30 min incubation. Azoxy-2-phenylethanewas identified by comparison of its chromatographic (thin-layer,high pressure liquid and gas chromatography) properties withthose of an authentic standard and was confirmed by mass spectrometry.The metabolism of phenylethylamine to azoxy-2-phenylethane appearscompletely dependent on the presence of divalent manganese;no reaction was observed in the absence of this metal or inthe presence of equivalent concentrations of cupric ions. Azoxy-2-phenylethanewas mutagenic, with S-9 activation, in S. typhimurium strainsTA 100 and TA 1535 but not in TA 98 or TA 1537. This reportconstitutes the first demonstration of the formation of an aliphaticazoxy compound from the corresponding amine by a mammalian system.