4-(4-nitrobenzyl)pyridine tests for alkylating agents following chemical oxidative activation
Thomas, John J.; Kim, J. H.; Mauro, D. M.
Thomas, J. J.; Kim, J. H.; Mauro, D. M.; (1992). "4-(4-nitrobenzyl)pyridine tests for alkylating agents following chemical oxidative activation." Archives of Environmental Contamination and Toxicology 22(2): 219-227. <http://hdl.handle.net/2027.42/48076>
AbstractA chemical activation system (CAS) designed to mimic the mammalian mixed-function oxidase enzymes was found to activate target compounds to reactive electrophiles. Activated compounds were assayed by reaction with 4-(4-nitrobenzyl)pyridine (NBP). A model nucleophile of 7-alkylguanine of nucleic acids, NBP produces a violet color following alkylation. Twenty compounds from several chemical classes were tested. The test generally gave positive and negative responses where expected. Two compounds, trichloroethylene and diethylnitrosamine, exhibited a linear Beer's law relationship in the concentration range tested. A high degree of linear correlation (r>0.97) was obtained for these compounds. Other compounds showed varying degrees of linear correlation from high correlation (r=0.94) to weak correlation (r=0.44). The CAS-NBP assay results were compared to bacterial mutagenicity and animal carcinogenicity test results when information was available. A good correlation (r=0.80) existed between direct alkylating activity and direct mutagenicity. Similar correlations existed between NBP alkylation following activation and mutagenicity following microsomal activation (r=0.73). Also, different correlations were observed between carcinogenicity and NBP alkylation following activation (r=0.69) and without activation (r=0.38).
Springer-Verlag; Springer-Verlag New York Inc.
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