Alpha-nitrosaminoaldehydes: highly reactive metabolites.
alpha-Nitrosamino aldehydes are highly reactive compounds which are directly-acting mutagens and are capable of facile transnitrosation to secondary and primary amines. The latter lead reactions to deamination. N-Nitrosobutyl(2-oxoethyl)amine (NBOEA) undergoes spontaneous decomposition in buffer at pH greater than 7 (25 degrees C) to give glyoxal and products implicating the formation of the butyl diazonium ion. NBOEA reacts with guanosine to produce xanthosine (by deamination), 7-butylguanosine and the 1,N2 glyoxal adduct, among other products. All beta-nitrosaminoethanols investigated undergo liver alcohol dehydrogenase-catalysed oxidation to their corresponding aldehydes. Several of these aldehydes have been shown to be directly-acting mutagens. These data provide strong evidence for an alternative carcinogenic bioactivation route for nitrosamines which does not involve alpha-oxidation.