Nucleic acid binding of arylamines during the respiratory burst of human granulocytes.
Following stimulation with phorbol myristate acetate, human granulocytes were found to incorporate a series of arylamines into cellular nucleic acid. No such binding occurred if the granulocytes were not induced to undergo the respiratory burst. The relative amount of covalent binding to cellular DNA and RNA was found to depend strongly on the chemical structure of the arylamine. 2-Aminofluorene gave the highest ratio of DNA/RNA binding, while 4-nitroaniline showed a very low ratio of DNA/RNA binding. 4-Nitroaniline may bind only to RNA, since the degree of binding to DNA was at the level of detectability. Two other substrates, 4-chloroaniline and 4-methylaniline, gave intermediary ratios of DNA/RNA binding. Studies on the possible role of the granulocyte enzyme myeloperoxidase in the activation and binding of these arylamines were conducted in vitro and also through the use of azide, an inhibitor of myeloperoxidase activity in cells. The results indicate that myeloperoxidase probably plays only a limited role in causing the covalent binding of arylamines to nucleic acid in human granulocytes. It is probable that other reactive oxygen species, which are not dependent upon myeloperoxidase for their production, are necessary for the bioactivation of some arylamines, especially for substrates such as 4-nitroaniline. A free-radical mechanism for arylamine bioactivation, and its potential role in arylamine toxicity, was presented in the context of the current scientific literature.
Corbett
M D
MD
Food Science and Human Nutrition Department, University of Florida, Gainesville 32611.
Corbett
B R
BR
D000814:Aniline Compounds / Q000097:blood / Q000378:metabolism*; D004247:DNA / Q000097:blood / Q000378:metabolism*; D005449:Fluorenes / Q000097:blood*; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009195:Peroxidase / Q000378:metabolism; D012313:RNA / Q000097:blood*; D016897:Respiratory Burst; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000814:Aniline Compounds; D005449:Fluorenes; C012177:2-aminofluorene; D012313:RNA; D004247:DNA; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate