The objective of this project is to investigate the mechanism(s) of tetranitromethane (TNM) pulmonary toxicity and carcinogenicity. This project includes studies of the reactions of TNM with cellular DNA and proteins, in vitro and in vivo. Analysis by capillary electrophoresis show a number of potentially altered nucleosides resulting from reaction of TNM with DNA. Because TNM specifically nitrates tyrosine residues on proteins, the effects of TNM on phosphorylation and dephosphorylation of membrane tyrosine residues, and subsequent effects on cell proliferation are being investigated. Preliminary in vitro studies indicate that phosphorylation of nitro-tyrosine is a very slow reaction. Similar studies are in progress to evaluate the nitration on the dephosphorylation of phosphotyrosine.
