Enhanced demethylation and denitrosation of N-nitrosodimethylamine by human liver microsomes from alcoholics.
The metabolism of N-nitrosodimethylamine (NDMA) was investigated in incubations with human liver microsomes from alcoholics and control patients who suffered from other diseases, but had a histological normal liver. All of the microsomal samples studied were able to metabolize NDMA at various concentrations to both formaldehyde and nitrite. Analysis of the liver microsomes from alcoholics revealed that both enzymatic activities--formaldehyde and nitrite formation--were enhanced several times as compared to the control patients. The results point to the fact that alcoholics metabolize NDMA at a higher rate probably due to the induction of one or more ethanol-inducible human liver cytochromes (cyt.) P450. The question if alcoholics therefore possess a higher risk for carcinogenic events is discussed.
Amelizad
S
S
Max von Pettenkofer Institut, Federal Health Office, Berlin F.R.G.
Appel
K E
KE
Schoepke
M
M
Rühl
C S
CS
Oesch
F
F
D000328:Adult; D000437:Alcoholism / Q000201:enzymology*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000201:enzymology*; D009573:Nitrites / Q000096:biosynthesis
D007527:Isoenzymes; D009573:Nitrites; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System; D004128:Dimethylnitrosamine