Induction of plasma acetylcholinesterase activity and apoptosis in mice treated with the organophosphorus toxicant, tri-o-cresyl phosphate

Abstract

Organophosphorus compounds (OP) inhibit acetylcholinesterase (AChE) activity and cause cultured cells to undergo apoptosis. Live mice treated with OP have reduced AChE activity, but after a short recovery period, their AChE activity rebounds to levels that exceed baseline by more than 2-fold. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals. Our goal was to determine whether induction of AChE activity is associated with apoptosis in live mice. For this purpose we treated mice with 1500 mg kg⁻¹ tri-o-cresyl phosphate. On day one after treatment their plasma AChE activity was inhibited by 50%. On day 4, plasma AChE activity rebounded to a level 2.2-fold higher than pretreatment activity and remained elevated for about two months. On day 4, AChE activity in the lung was 1.5-fold higher than in controls. Cells in lung sections that were positive in the apoptosis TUNEL assay, stained heavily for AChE activity. In conclusion, AChE activity and apoptosis are induced in mice treated with tri-o-cresyl phosphate. Unusually high AChE activity may be a marker of exposure to apoptosis-inducing substances.