Metabolism and macromolecular binding of 1-nitronaphthalene in the mouse

Toxicology
R E Rasmussen

Abstract

The metabolism and binding of 1-nitronaphthalene (1-NN) to tissue macromolecules was studied in the mouse using tissue microsomes, lung slices, and isolated lung cells. With microsomes, binding was NADPH-dependent. CO inhibited binding in lung microsomes by more than 90% and in liver microsomes by 60-85%. Nitrogen inhibited binding by 70-80% in lung microsomes and 50-75% in liver microsomes. Incubation of the microsomes in pure O2 did not affect the binding of 1-NN. SKF525A inhibited binding in a dose-dependent manner with approximately 50% inhibition of binding obtained at a molar ratio of 1:4, SKF525A/1-NN. The rate of 1-NN binding by liver microsomes was increased by pretreatment of the mice with phenobarbital (1.2 vs. 0.8 nmol/min/mg protein). beta-Naphthoflavone (BNF) pretreatment increased slightly the rate of 1-NN binding by lung microsomes (1.2 vs 0.9 nmol/min/mg protein), but had no effect on binding by liver microsomes. Studies with isolated lung cells indicated that cell cultures enriched in Clara cells were 6-15-fold more active in metabolism and binding of 1-NN than cultures not containing Clara cells. Autoradiography of lung slices incubated in vitro with [14C]1-NN showed the label to be concentrated in the cells ...Continue Reading

Citations

Jan 1, 1995·Life Sciences·A R ParrishK Brendel
Nov 25, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K RiddC J Reed
Apr 1, 1990·Environmental Health Perspectives·R D Verschoyle, D Dinsdale
Feb 8, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kimberly C DayMichelle V Fanucchi

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