Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450 |
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| Authors: | C S Yang D R Koop T Y Wang M J Coon |
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| Affiliation: | 1. Department of Cardiac Surgery, Affiliated Hospital, Guizhou Medical University, Guiyang, China;2. Department of Vascular Surgery, Central Hospital of Dalian University of Technology, Dalian, China;3. School of Life and Pharmaceutical Science, Dalian University of Technology, Panjin, China;4. Department of Vascular Surgery, Shanghai Ninth People''s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;5. School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia |
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| Abstract: | The ethanol-induced rabbit liver microsomal cytochrome P-450, P-450LM3a, has been shown previously to efficiently catalyze the demethylation of N-nitrosodimethylamine (NDMA) with a Km of 2.9 mM. Since the predominant Km in hepatic microsomes from ethanol-treated rabbits is 0.07 mM, the role of P-450LM3a in the activation of this carcinogen has been uncertain. In the present study, antibodies to P-450LM3a were shown to almost completely inhibit NDMA demethylation by the purified P-450 in a reconstituted system as well as the low-Km activity of liver microsomes from control or ethanol-treated rabbits. In contrast, the antibody did not inhibit the high-Km NDMA demethylase activity in the microsomes. These results indicate that P-450LM3a is the major P-450 responsible for the low-Km NDMA demethylase activity. In addition, evidence is provided for the existence of a cytochrome immunochemically similar to P-450LM3a in liver microsomes from rats, mice, and guinea pigs that effectively catalyzes the demethylation of NDMA. |
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