| 3130202 |
Iba MM, Thomas PE: Activation of 3,3'-dichlorobenzidine in rat liver microsomes to mutagens: involvement of cytochrome P-450d. Carcinogenesis. 1988 May;9(5):717-23.
Studies were carried out, using antibodies to specific cytochrome P-450 isozymes, to identify the isozymes involved in the NADPH-dependent activation of 3,3'-dichlorobenzidine (DCB) by rat hepatic microsomes to mutagens in the Ames test. DCB activation was not affected by a monoclonal antibody specific for P-450c or by a monoclonal antibody specific for P-450b, but was inhibited 69% by a polyclonal antibody made against P-450d. DCB activation was also inhibited 46% by antibody specific for NADPH-cytochrome P-450 reductase. Further, addition of methimazole, a high affinity substrate for the flavin-containing monooxygenase, reduced the residual mutagenicity in the systems containing antibody to P-450d and cytochrome P-450 reductase to 9% and 19%, respectively, of the appropriate control values. It is concluded that P-450d contributes to a majority of the P-450-dependent activation of DCB in hepatic microsomes. The results also suggest that the flavin-containing monooxygenase may contribute to the microsomal activation of DCB. |
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