Cytochrome P-450-dependent formation of ethylene from N-nitrosoethylamines

Ethylene was identified as a metabolite of N-nitrosodiethylamine (NDEA) as well as of N-nitrosomethylethylamine and N-nitrosoethylbutylamine. The formation of ethylene from these carcinogenic compounds is cytochrome P-450- and NADPH-dependent. With NDEA, the rate of the reaction in rabbit liver microsomes is increased by treatment of the animals with phenobarbital or ethanol, which are known to induce the synthesis of P-450 form 2 and P-450 form 3a (p-450(ALC)) respectively, and the activity is inhibited by anti-P-450 form 2 or form 3a IgG. The rate of ethylene formation is about 10-fold higher in nasal microsomes than in hepatic microsomes. In a reconstituted system, P-450 form 3a is the most active in ethylene formation from NDEA, followed by forms 2 and 4. It has been proposed by other that the α-hydroxylation of N-nitrosodialkylamines leads to the formation of an aldehyde and an alkyl diazonium ion, which, with the loss of N₂, yields an alkyl carbonium ion capable of producing the corresponding alcohol or binding macromolecules through electrophilic reactions. In the case of the N-nitrosoalkylethylamines we have studied, the ethyl carbonium ion produced could, in addition, generate ethylene by proton elimination.