Hydroxylation of carbon atoms of the alkyl chain of symmetrical N-nitrosodialkylamines by rat liver microsomes.
Liver microsomal preparations from control and treated rats (cytochromes P450 1A, 2B, 3A and 2E1-induced) metabolized at variable metabolic rates three nitrosodialkylamines (N-nitroso-dipropyl, dibutyl and diamyl-amines) into aldehydes and hydroxy-nitrosamines. The longer the alkyl chain, the smaller was the metabolic rate of the alpha-hydroxylation of alkyl chain yielding aldehyde and the greater was the metabolic rate of the corresponding (omega-1)-hydroxyl metabolite formation. Thus, the (omega-1) hydroxylation of the alkyl chain was the major metabolic pathway of N-nitrosodiamylamine (NDAA) so far as it represented 22-fold the alpha-hydroxylation. The balance between beta to omega hydroxylation and alpha-hydroxylation depends upon the alkyl chain length and also on specific P450 isoform induction.
Bellec
G
G
Laboratoire de Biochimie, Faculté de Médecine, Brest, France.
Dreano
Y
Y
Pichon
R
R
Ménez
J F
JF
Berthou
F
F
D000818:Animals; D002244:Carbon / Q000378:metabolism; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism*; D009602:Nitrosamines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
D002273:Carcinogens; D009602:Nitrosamines; D002244:Carbon