Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.

Abstract:

:Macrophages and their immortalized cell lines can be activated to form nitrite and nitrate via oxidation of arginine and this is accompanied by the formation of N-nitroso compounds. The mechanism of nitrosamine formation has been investigated through the use of compounds which are known either to inhibit or enhance acid-catalyzed nitrosation. The range of nitrogen acceptors has been expanded to include ureas as well as amines of varying pKa and structure. The results are consistent with a mechanism in which NO is oxidized to N2O3 and N2O4, which are capable of nitrosating amines, but not ureas or amides, at neutral pH. This is in agreement with a recent observation that macrophage cell-free extracts can oxidize arginine to NO. The effect of ascorbic acid on intact activated macrophages is complex since nitrite formation is enhanced over a very wide range of ascorbate concentrations (5-500 microM) while nitrosation is inhibited at ascorbate concentrations greater than 50 microM.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Kosaka H,Wishnok JS,Miwa M,Leaf CD,Tannenbaum SR

doi

10.1093/carcin/10.3.563

subject

Has Abstract

pub_date

1989-03-01 00:00:00

pages

563-6

issue

3

eissn

0143-3334

issn

1460-2180

journal_volume

10

pub_type

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