Serum carboxylesterase activity in various strains of rats: sensitivity to inhibition by CBDP (2-/o-cresyl/4H:1:3:2-benzodioxaphosphorin-2-oxide).
Rodents are relatively insensitive to the neurotoxic effects of various organophosphorus compounds. The purpose of this investigation was to determine if differences in inactivation of CBDP could explain the strain differences in the sensitivity to neurotoxicity following administration of TOCP (tri-o-cresyl phosphate) observed by Carrington and Abou-Donia (1988). Serum carboxylesterase but not cholinesterase is an important detoxification route for organophosphates. Serum carboxylesterase and cholinesterase activity were significantly different (p less than 0.05) among the various strains of rats. The rank order of carboxylesterase activity was Sprague Dawley (6158 nmole/ml serum/min) greater than Long Evans (5589) greater than Fischer 344 (5010) whereas the rank order for cholinesterase activity was Fischer 344 greater than Sprague Dawley greater than Long Evans. TOCP is metabolized to the active neurotoxicant CBDP (2-/o-cresyl/4H:1:3:2-benzodioxaphosphorin-2-oxide). The ED50 for CBDP inhibition of serum carboxylesterase activity was found to vary considerably for the various strains of rats. The rank order of CBDP ED50 concentration in the various strains was Fischer 344 (437 microM) greater than Long Evans (339 microM) greater than Sprague Dawley (78 microM), indicating that there was a difference between the carboxylesterase of the various strains with regard to interaction with CBDP. It is suggested that the differences in the quantity of serum carboxylesterase combined with the differences in the interaction of the inhibitor with the enzyme(s) may be responsible for the strain differences observed by Carrington and Abou-Donia (1988).
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta, Canada.
J G
JG
Clement
N
N
Erhardt
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000097:blood*; D002802:Cholinesterases / Q000097:blood; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014317:Tritolyl Phosphates / Q000633:toxicity
D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D002265:Carboxylic Ester Hydrolases; D002802:Cholinesterases; C025541:tri-o-cresyl phosphate