ACTIVATION OF ENVIRONMENTAL CHEMICALS BY HEPATOCYTES

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The objectives of this study are to examine the activation of precarcinogens to reactive DNA binding and mutagenic metabolites in hepatocytes and S9. 1. The hepatocarcinogen, 2,4-diaminotoluene(DAT), was activated to reactive metabolites which bound to DNA to a greater extent than the nonhepatocarcinogen, 2,6-DAT. The ability of activation to mutagens and DNA binding species was examined. Inhibitors of metabolism were also examined. 2. The ability of constitutive isozymes of P-450 to activate a variety of mutagens was compared. 3. We also evaluated a human cell line, Hep G2, using antibodies to several human P-450s to determine whether the cell line resembled normal human liver cells in its metabolic capability. The goal of this project is to investigate the ability of various liver pathways to activate precarcinogens and to reactive DNA-binding and mutagenic species. The enzymatic composition of a human cell line was compared with that of normal liver to determine whether this human cell line could be expected to metabolize foreign chemicals in a manner similar to normal human liver.