The influence of triorthocresylphosphate on the distribution of 32P in the body of the rat after the injection of 32P-sarin
Medisch Biologisch Labortorium TNO
The ChE- and AE- activities and the 32P-concentration of the plasma from rats 1 and 24 hr after s.c. injection of 32P-sarin (200 μg kg) were measured. One hr after the injection the ChE was inhibited to approx. 10 per cent and the AE to 40-50 per cent; 23 hr later 50 per cent of the ChE activity was found to be restored and the AE had recovered its full activity. One hr after the 32P-sarin injection about 12 per cent of the injected amount of 32P was circulating in the blood plasma, but 23 hr later the radio-activity had disappeared nearly completely from the plasma. Pretreatment of rats with TOCP, an irreversible inhibitor of the plasma AE, enhanced the toxicity of sarin 6-8 times. It also produced a shift of the radioactivity found in the body of the rat 1 hr after the injection of 32P-sarin from the plasma to the brain, the muscles, the lungs and the kidneys. Serum from normal and from TOCP treated rats was incubated with 32P-sarin in different concentrations and thereafter filtered through Sephadex columns in order to determine the amounts of 32P-sarin attached to the proteins in the serum. It appeared that the proteins in the serum from TOCP treated rats had lost a considerable part of their 32P-sarin binding capacity. Electrophoresis of serum from a rat injected with 32P-sarin on cellulose-acetate and subsequent autoradiography of the cellulose-acetate strip showed radioactivity localised on a spot with AE- activity. It was concluded that the plasma proteins with which the 32P-sarin combined were identical with AE. The sarin binding capacity of the plasma AE was, however, considered to be too small to fully account for the enhanced toxicity of sarin for rats treated with TOCP. Non-specific sarin binding sites with affinity for TOCP elsewhere in the body were postulated. © 1969.
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Biochemical Pharmacology, 18 (18), 813-820