Effect of antibodies against cytochrome P-450 on demethylation and denitrosation of N-nitrosodimethylamine and N-nitrosomethylaniline.

Rat liver microsomes which were induced either with ethanol or PB were incubated with NDMA or NMA. Formaldehyde generation and nitrite formation were measured as metabolic parameters for oxidative bioactivation and denitrosation, respectively. The influence of antiserum PB3a1 and PB22 containing antibodies against the corresponding cytochrome P-450 species on both metabolic functions was investigated. The results showed that the influence on formaldehyde production and denitrosation varied independently in that both parameters were either not affected, or influenced in an opposite way, or inhibited to a different degree. Especially remarkable was the 80% inhibition of formaldehyde generation accompanied by no change in the nitrite formation by antiserum PB3a in ethanol-induced microsomes when NDMA was used as substrate. The 80% inhibition of formaldehyde production by antiserum PB3a was in contrast to no inhibition by antiserum PB2 under the same conditions. Denitrosation of NMA by PB-induced microsomes was inhibited by antiserum PB3a, but activated by antiserum PB2. It is concluded that oxidative demethylation and reductive denitrosation can be mediated by different cytochrome P-450 forms.