Incubation of phenylethylamine with rabbit liver microsomes, divalent manganese and a NADPH generating system leads to the formation of azoxy-2-phenylethane, among other metabolic products. Approximately 38 nmol of the azoxy compound is formed from 10 μmol of phenylethylamine during a 30 min incubation. Azoxy-2-phenylethane was identified by comparison of its chromatographic (thin-layer, high pressure liquid and gas chromatography) properties with those of an authentic standard and was confirmed by mass spectrometry. The metabolism of phenylethylamine to azoxy-2-phenylethane appears completely dependent on the presence of divalent manganese; no reaction was observed in the absence of this metal or in the presence of equivalent concentrations of cupric ions. Azoxy-2-phenylethane was mutagenic, with S-9 activation, in S. typhimurium strains TA 100 and TA 1535 but not in TA 98 or TA 1537. This report constitutes the first demonstration of the formation of an aliphatic azoxy compound from the corresponding amine by a mammalian system.
Bibliographical noteFunding Information:
This work was supported, in part, by Grant CA 15400 from the National Cancer Institute through the National Large Bowel Cancer Project. The interest and advice of Dr J.H.Weisburger is gratefully acknowledged. We thank Joseph Camanzo for performing the GC/MS analyses.