The influence of very low doses of N-nitrosodimethylamine (NDMA) on the apoptosis of rat neutrophils in vivo. The role of reactive oxygen species

N-nitrosodimethylamine (NDMA) causes the apoptosis of neutrophils in vitro experiments. This compound also has the ability to stimulate neutrophils fo r the production of reactive oxygen species. It has been decided to examine more closely whether the apoptosis of neutrophils by NDMA is caused by the influence of the radicals produced by these cells and whether the stimulat ion to undergo apoptosis of neutrophils is caused by NDMA in either the ori ginal form or by its metabolites. The experiment was conducted on rats. The animals were administered a one-time dose of NDMA intragastrically, 1.5 mg /kg. The research was conducted 1, 2, 4, 12 h consecutively following NDMA administration. The concentration of NDMA in blood was evaluated by means o f the gas chromatography method. The neutrophils were isolated from blood b y means of differential centrifugation. Respiratory burst was assessed in c ells, by means of the cytochrome c reduction method. The percentage of cell s revealing morphological properties of apoptosis was determined under the fluorescent microscope. It has been observed that the activation of the res piratory burst is caused mainly by non-metabolised NDMA. Probably the non-m etabolised molecules of this compound also have a decisive role in the init iation of apoptosis of neutrophils. It can be assumed that the main factor responsible for the apoptosis of neutrophil rats following a one-time NDMA administration is the induction of respiratory burst in neutrophils by this compound. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.