Fluorocarbon Toxicant Action on a Membrane Channel, Effects of Formycin Derivatives, Cell Recovery, and Detoxification.
Abstract
Treatment of L5178Y mouse lymphoma cells with perfluoro-n-decanoic acid (PFDAS) at 30 C produced inactivation of a channel in the cell membrane; activity of the channel was estimated from the efflux of 2-aminopurine (AP). The cells were preloaded with 100 micromoles AP, put in a flow system, and AP efflux was estimated continuously at 21 C from the fluorescence emission of AP at 370 nm. The initial rate of AP efflux for control cells increased with AP was inhibited by the presence of uric acid in the external buffer with an apparent inhibition constant value of 355 micromoles for urate. These observations indicate a urate-sensitive channel for AP in the membrane of L5178Y cells. The AP channel was markedly inactivated by 150 micrograms/m1 PFDA for 24 hr at 30 C. There was no significant recovery of AP flux after 3 days at 30 C in fresh growth medium; however, recovery was significant after 6 days. Recovery of activity of the AP channel occurred in one day at 37 C. Cell recovery studies were continued by experiments to show the effect of the drug dilazep on the recovery of L5178Y cells from treatment with three nucleoside toxins. A one-day treatment at 37 C with formycin A, formycin B, or 5'deoxyformycin A produced an arrest in cell growth. The capacity for cell division recovered during two additional days of incubation at 37 C. Cell recovery from each of the three formycin derivatives was accelerated by a simultaneous treatment with dilazep. The cell recovery technique is suggested as potential procedure to demonstrate toxicant selectivity for different cell types.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 16, 1986
- Accession Number
- ADA173212
Entities
People
- Paul W. Wigler
Organizations
- University of Tennessee