Effect of metabolism on the anticholinesterase activity of parathion and paraoxon in primary neuron cultures.
The anticholinesterase activity of parathion and paraoxon, and the effects of metabolism on this activity, were examined in primary cultures of chick embryo forebrain neurons. Paraoxon was an extremely potent inhibitor of acetylcholinesterase activity, with a median inhibitory concentration (IC(50)) more than 800 times more potent than parathion. Incubation of these two compounds with rat hepatic S-9 fractions, before neuron treatment, dramatically altered their activity, though with opposite effects. Parathion, when preincubated with control S-9 (from saline-treated rats), exhibited increased anticholinesterase activity, whereas paraoxon was much decreased in potency. The relative anticholinesterase activity of these compounds after incubation with the control S-9 fractions was much more predictive of the relative toxicites of these compounds in vivo. Preincubation of these compounds with hepatic S-9 fractions that had been obtained from rats induced with either phenobarbitone or 3-methylcholanthrene, resulted in a decreased activation of parathion and an increased deactivation of paraoxon compared with control S-9.
Sawyer
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TW
Biomedical Defence Section, Defence Research Establishment Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6.
Weiss
M T
MT
Dickinson
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T