Comparative Biochemistry and Metabolism. Part 2. Naphthalene Lung Toxicity.

Abstract

The studies reported in this document were to quantitatively examine the diffusion of naphthalene oxide and reactive metabolites form naphthalene in suspensions of isolated mouse hepatocytes and to determine whether the efflux of these metabolites was dependent upon the depletion of intracellular glutathione. The efflux of naphthalene oxide from intact hepatocytes was monitored in incubations containing 3H-glutathione (this tripeptide will not cross the intact hepatocellular membrane) and was based on the measurement of 3H-labelled glutathione adducts. Between 17 and 35% of the total naphthalene oxide formed during the metabolism of naphthalene in the cell was trapped on the exterior of the cell with 3H-glutathione. The fraction of epoxide exiting the hepatocytes as a percentage of the total amount formed did not vary with increasing naphthalene concentrations between 0.005 and 1.5 mM. These data in conjunction with the studies showing that incubation of hepatocytes with naphthalene at concentrations of 0.05 mM or greater caused a significant depletion of intracellular glutathione, suggested that the quantity of naphthalene oxide diffusing as a percentage of the total formed was not dependent upon the intracellular glutathione status. In contrast, the ration of extracellular vs intracellular covalent binding was dependent on the concentration of naphthalene in the incubation.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 1985
Accession Number
ADA163144

Entities

People

  • Alan R. Buckpitt
  • Paul R. Richieri

Organizations

  • University of California, Irvine

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  • Biomedical

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  • Biology

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