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4-(4-nitrobenzyl)pyridine tests for alkylating agents following chemical oxidative activation

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Abstract

A 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).

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Authors and Affiliations

  1. Department of Biological Sciences, Florida Institute of Technology, 32901, Melbourne, Florida, USA

    J. J. Thomas & D. M. Mauro

  2. Environmental Chemistry Program, Department of Environmental and Industrial Health, School of Public Health, The University of Michigan, 48109, Ann Arbor, Michigan, USA

    J. H. Kim

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  1. J. J. Thomas
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  2. J. H. Kim
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  3. D. M. Mauro
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Thomas, J.J., Kim, J.H. & Mauro, D.M. 4-(4-nitrobenzyl)pyridine tests for alkylating agents following chemical oxidative activation. Arch. Environ. Contam. Toxicol. 22, 219–227 (1992). https://doi.org/10.1007/BF00213289

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  • DOI: https://doi.org/10.1007/BF00213289

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