M. Ehrich et L. Correll, INHIBITION OF CARBOXYLESTERASES IN SH-SY5Y HUMAN AND NB41A3 MOUSE NEUROBLASTOMA-CELLS BY ORGANOPHOSPHORUS ESTERS, Journal of toxicology and environmental health. Part A, 53(5), 1998, pp. 385-399
Carboxylesterases (CbxE) can be inhibited by organophosphorus esters (
OPs) without causing clinical evidence of toxicity. CbxE are thought t
o protect the critical enzyme acetylcholinesterase (AChE) from OP inhi
bition in animals. CbxE and AChE are both present in neuroblastoma cel
ls, but, even though these cells have potential to be an in vitro mode
l of OP toxicity, the effect of OPs on CbxE and the relationship of Cb
xE inhibition and AChE inhibition have not yet been examined in these
cells. Therefore, this study examined concentration-related OP-induced
inhibition of CbxE in human SH-SY5Y and mouse NB41A3 neuroblastoma ce
lls with 11 active esterase inhibitors: paraoxon, malaoxon, chlorpyrif
os-oxon, tolyl saligenin phosphate (TSP), phenyl saligenin phosphate (
PSP), diisopropyl phosphorofluoridate (DFP), mipafox dichlorvos, trich
lorfon, dibutyryl dichlorovinyl phosphate (DBVP), and dioctyl dichloro
vinyl phosphate (DOVP). AN could inhibit CbxE, although the enzyme was
less likely to be inhibited than AChE following exposure to 9 of the
test compounds in the human cell line and to all 11 of the test compou
nds in the murine cell line. Species differences in concentration-rela
ted inhibitions of CbxE were evident. When cells were exposed first to
an OP with a low IC50 toward CbxE (PSP), followed by an OP with high
affinity for AChE (paraoxon or malaoxon), inhibitions of CbxE and AChE
were additive. This indicated that CbxE did not protect AChE from OP-
induced inhibition in this cell culture model.