F. Guengerich
Oct 15, 1977
Citations
0
Influential Citations
43
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract 2-( N -ethylcarbamoylhydroxymethyl)furan was studied as a simple model for the entire class of toxic furans. This compound is toxic to both the lung and liver of the rat—covalent binding occurs predominantly in these target organs. The model was covalently bound to protein and nucleic acids throughout the cell; the enzymes responsible for activating the compound to a form(s) capable of covalently binding to these tissue macromolecules are localized in the microsomal and, to a much lesser extent, nuclear fractions of the cells of the target organs. Binding and toxicity appear to involve the furan moiety of the compound; this binding can be inhibited by added nucleophiles, but not by epoxide hydrase inhibitors. Studies utilizing both microsomes and highly purified reconstituted cytochrome P-450 systems for activation indicate that the reactive metabolite(s) possesses a certain amount of stability, in agreement with the observed distribution of the compound in vivo .