Denitrosation of N-nitrosomorpholine by liver microsomes; possible role of cytochrome P-450.

Liver microsomes from male mice and rats were incubated with N-nitrosomorpholine (MoNA) and an NADPH-regenerating system. The formation of nitrite was measured after induction or inhibition of the microsomal monooxygenase system. Pretreatment of the animals with phenobarbital (PB) enhanced nitrite formation by about 200%, while 3-methylcholanthrene (3-MC)-induction showed no exceptional effects. Various specific inhibitors of the monooxygenase function including carbon monoxide decreased nitrite formation. In conjunction with results obtained by spectra studies it is suggested that N-nitrosomorpholine is denitrosated by a reduction process in which cytochrome (cyt.) P-450 seems to be involved. Nitricoxide formed is partly converted to nitrite under these conditions.