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Organophosphate-induced acetylcholinesterase inhibition and embryonic retinal cell necrosis in vivo in the teleost (Oryzias latipes).

Authors
Hamm-JT; Wilson-BW; Hinton-DE
Source
Neurotoxicology 1998 Dec; 19(6):853-869
NIOSHTIC No.
20033260
Abstract
Recent monitoring of the Sacramento-San Joaquin River system (CA) indicates that levels of the organophosphate pesticide, diazinon, exceed National Academy of Science guidelines and these levels result in toxicity in USEPA acute toxicity tests with Ceriodaphnia dubia. Since organophosphates (OPs) inhibit acetylcholinesterase (AChE), the present study examined the effects of diazinon on the embryonic nervous system of a model teleost, medaka, Oryzias latipes. Preliminary histological screens revealed limited retinal cell necrosis in control embryos with apparent increased necrosis in diazinon-exposed embryos. Subsequently, embryos were exposed to 1.8 x 10(-5), 4.4 x 10(-5), or to 8.8 x 10(-5) M diazinon and replicates were frozen for biochemical analysis or were fixed for histopathological analysis at days 3, 5, and 7 of development. Diazinon exposure significantly inhibited AChE activity within whole embryos and in homogenates of retinas from treated animals. Histological examination of embryos indicated that as the retina underwent differentiation into distinct cell layers, between days 5 and 7, small foci of necrotic cells became apparent within the inner nuclear layer and isolated individual pyknotic cells were observed in the ganglion layer. Quantification of foci of necrotic cells revealed that 8.8 x 10(-5) M diazinon increased number and area of these lesions. Enzyme histochemistry localized AChE activity to regions equivalent to sites of necrosis. Separate exposures of embryos to the OP, diisopropylphosphorofluoridate, produced large foci of necrotic cells at sites equivalent to those seen following diazinon exposure.
Keywords
Acetylcholinesterase; Retinal-disorders; Chemical-analysis; Chemical-hypersensitivity; Chemical-inhibition; Chemical-reactions; Chemical-synthesis; Nervous-system; Nervous-system-disorders; Nervous-system-function; Histology; Histomorphology; Histopathology; Cell-alteration; Cell-biology; Cell-damage; Cell-function; Embryology; Embryopathology; Embryotoxicity; Exposure-levels; Exposure-limits; Biochemical-analysis; Biochemical-tests; Enzymatic-disorders; Enzymatic-effects; Enzyme-activity; Enzymes; Enzymology; Diazo-compounds
Contact
J. T. Hamm, School of Veterinary Medicine, Department of Anatomy, Physiology, and Cell Biology, University of California, Davis 95616
CODEN
NRTXDN
Publication Date
19981201
Document Type
Journal Article
Funding Amount
1055222
Funding Type
Cooperative Agreement
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U07-CCU-906162
Issue of Publication
6
ISSN
0161-813X
Source Name
Neurotoxicology
State
CA
Performing Organization
University of California - Davis
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