Effect of O₂ tension on the bioactivation and metabolism of aliphatic halides by primary rat-hepatocyte cultures

A. B. Direnzo Departments of Anesthesiology and Pharmacology, University of Arizons, Tucson, AZ, 85724, USA

A. J. Gandolf Departments of Anesthesiology and Pharmacology, University of Arizons, Tucson, AZ, 85724, USA

I. G. Sipes Departments of Anesthesiology and Pharmacology, University of Arizons, Tucson, AZ, 85724, USA

K. Brendel Departments of Anesthesiology and Pharmacology, University of Arizons, Tucson, AZ, 85724, USA

J. L. Byard Department of Environmental Toxicology, University of California, Davis, CA, 95616, USA

Abstract

1. The covalent binding of CCl₄ and CF₃CHBrCl to cultured rat hepatocytes was enhanced by anoxic conditions, indicative of enhanced reductive biotransformation.

2. The covalent binding of CHCl₃ and CHCl₂CH₂Cl decreased as the O₂ concentration was decreased, indicating a preference for oxidative metabolism.

3. Lower O₂ tensions decreased the formation of polar water-soluble metabolites with CHCl₃ and CHCl₂CH₂Cl, while CCl₄ and CF₃CHBrCl were unaffected.

4. The results indicate that primary cultured hepatocytes can reductively biotransform and bioactivate aliphatic halides under anoxic conditions.

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Effect of O₂ tension on the bioactivation and metabolism of aliphatic halides by primary rat-hepatocyte cultures

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Effect of O₂ tension on the bioactivation and metabolism of aliphatic halides by primary rat-hepatocyte cultures