Inactivation of Cholinesterases by Gamma Radiation

¹ From the Health Division, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico

Animals and in vitro preparations of cholinesterase were exposed to massive doses of gamma radiation from a barium-lanthanum source and from two x-ray sources. The cholinesterase activity and the activity-pS kinetics of rat brain were unaffected by an in vivo dose of 60,000 r from the isotope source. The animals were in violent convulsion and had severe diarrhea at the time they were killed. The activity of whole human plasma was unaffected by 100,000 r of 1000-kvp x-rays. Dilute hemolysate of human blood in 0.1% gelatin was inactivated 10% by 150,000 r of 250-kvp x-rays. Purified cholinesesterase in dilute sheep serum was inactivated at a rate of 15%/100,000 r of 250-kvp x-rays. In m/15 phosphate buffer containing 0.1% bacteriological gelatin it was inactivated at a rate of 50%/100,000 r from the isotope source. In buffer alone it was inactivated at a rate of 21%/10,000 r from the isotope source. The relationship between dose and effect appears to be linear, and this is attributed to the very low concentration of enzyme molecules which makes the probability of a second hit negligible. The gradation of protection is regarded as a nonspecific effect, a function of the concentration of large molecules which compete for the ionization. The enzyme was not protected by a high concentration of its substrate. While the enzyme can be inactivated by gamma irradiation, the conditions required are so different from those found in the intact animal that the signs and symptoms resembling cholinergic manifestations observed with supralethal doses cannot be explained in terms of inactivation of cholinesterase by the radiation.

Note:
with the technical assistance of Dorothy J. Nickolai and Helen M. Miller