| Abstrakt: |
Six alkylnitmamino ethanols (R-N(N0)-CHCH0H; R = Me, nBu, sBu, iBu, tBu, HOCHCH), including the potent carcinogen -nitrosodiethanolamine, have been shown to undergo efficient liver alcohol dehydrogenase catalyzed oxidation to their corresponding α-nitrosamino aldehydes. Five structurally representative nitrosamino-ethanals (RN( NO)CHCH0, R = 4-ClCH-, CH-, nBu-, tBu-, HOCHCH-) have been synthesized. Each of these compounds demonstrates the unusual property of facile transnirosation to a secondary amine. Transnitrosation to dimethylamhe, pyrrolidine, morpholine and -methylanlline has been shown. This reaction occurs rapidly at room temperature in organic solvents but is somewhat slower in aqueous buffer due to extensive equitibrium formation of gem diols by hydration of the aldehyde group. In aqueous media the transnitrosation rate increases with increasing pH from 7to9anddoesnotocavatpH4.Transnitrosationtoprimary amines results in deamination (benzylamine → benzyl alcohol). The transnitrosation reaction is accompanied by the formation of imines of glyoxal (R - N = CH - CH = N - R) which appear as primary amines and glyoxal in aqueous sdution. Other products have also been characterized as well. These chmical and biochemical data, taken together with results in other laboratories, provide strong support for our hyppothesis that certin β-oxidized nitrosamines can be activated to proximate or ultimate carcinogens by biochemical oxidation to produce highly reactive nitrosamines. [ABSTRACT FROM PUBLISHER] |
