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Organophosphate Inhibition of Nematode Esterases And ORGANOPHOSPHATE INHIBITION OF NEMATODE ESTERASES AND INTERACTION WITH CHLORINATED HYDROCARBON INSECTICIDES By DONALD S. CANNON A Dissertation submitted to the Graduate School-New Brunswick Rutgers, The State University of New Jersey in partial fulfillment of the requirements for the degree of Doctor of Philosophy Graduate Program in Entomology written under the direction of Professor W.R. Jenkins and approved by W.R. Jenkins Andrew Forgash Dwight Taylor New Brunswick, New Jersey January 2009 ABSTRACT OF THE DISSERTATION Organophosphate Inhibition of Nematode Esterases and Interaction with Chlorinated Hydrocarbon Insecticides by Donald S. Cannon Dissertation Director: W.R. Jenkins The discovery and subsequent development of a vast array of synthetic organic pesticides has provided nematologists with a rich source of potential nematicides. Certain types of insecticides, notably the organophosphates and more recently the carbamates, have been of significant value in nematode control, whereas, the chlorinated hydrocarbon insecticides are generally ineffective. The wide discrepancy in the chemical structure-toxicity relationship between these two phytogenetically separate animals serves to emphasize the need for greater understanding of nematode chemistry and physiology. Development of a sophisticated nematicide technology requires greater knowledge of nematode response to toxic and non-toxic chemicals. In this study, investigations were carried out into nematode esterase inhibition by a nematicidal organophosphate and the interactions with chlorinated hydrocarbon insecticides. Phorate suppression of esterase activity and the interference by chlorinated hydrocarbon insecticides were studied in whole homogenates of the free-living nematodes Panagrellus redivivus and the plant parasitic species Ditylenchus dipsaci and on their electrohporetically isolated enzymes. ii The NE enzymes of P. redivivus were somewhat more sensitive than cholinesterases (ChE) to phorate with pI50 values (negative log of the molar concentration inhibiting activity 50%) were 5.4 and 3.7 respectively. Greater resistance and more rapid recovery from NE inhibition by the organophosphate was demonstrated in homogenates of D. dipsaci. A comparison of the inhibition curves of both species indicates phorate to be moderately toxic to NE activity in vitro, approximately one-tenth that of the standard organophosphate paraoxon and slightly more inhibitory than the anti-ChE carbamate eserine. Seven of the eight esterases of P. redivivus and one of the three isolated from homogenate of D. dipsaci were inhibited to varying degrees by phorate and the two standard inhibitors. The pattern of relative degree of sensitivity among the esterases was similar for the two organophosphates but differed with the carbamate eserine. Homogenates pretreated with one of four chlorinated hydrocarbon insecticides, chlordane, DDT, dieldrin, or lindane, reduced the antiesterase toxicity of 5 x 10-7M concentration of phorate 26, 18, 20, and 12% (P. redivivus), respectively. Reduction of inhibition by 10-3M concentration of chlordane increased inversely with phorate concentration in homogenates of both species. A similar reduction, but to a higher degree, was produced by pretreatment of homogenates with the microsomal stimulant phenobarbitol. Both chlordane and phenobarbitol reduced esterase inhibition by the carbamate nematicide aldicarb but had no effect on eserine toxicity. Electrophoretically isolated esterases of P. redivivus were not protected from phorate inhibition by pretreatment with chlordane. iii In an in vivo assay no reduction of phorate toxicity was found in P. redivivus cultured in insecticide treated oatmeal or presoaked in an aqueous solution of the insecticide. Chlorinated hydrocarbon insecticides appear to stimulate microsomal release of aliesterases capable of hydrolyzing organophosphates in a manner similar to the interaction phenomena occurring in rats and mice. iv TABLE OF CONTENTS Abstract............................................................................................................................... ii List of Tables .................................................................................................................... vii List of Figures.................................................................................................................... ix Introduction..........................................................................................................................1 Objectives ............................................................................................................................4 Literature Review.................................................................................................................5 Esterases.........................................................................................................................5 Physiological role...........................................................................................................5 Nematode esterases........................................................................................................6 Organophosphate inhibition...........................................................................................7 Methods and Materials.......................................................................................................11 Quantitative colorimetric analysis ...............................................................................12 Disc electrophoretic analysis .......................................................................................20 Chemical Materials ............................................................................................................25 Results and Discussion ......................................................................................................27 Factors influencing esterase activity............................................................................29 Inhibition of esterase activity.......................................................................................30 Esterase recovery from phorate inhibition...................................................................41 Inhibition studies on separated esterases .....................................................................42 Preparatory studies.......................................................................................................46 Inhibition of isolated esterases.....................................................................................46 Insecticide interaction with phorate.............................................................................49 v TABLE OF CONTENTS (continued) Summary and Conclusions ................................................................................................61 Literature Cited ..................................................................................................................63 Curriculum Vita .................................................................................................................66 vi LIST OF TABLES Table 1. The wet, dry, and protein weights of Panagrellus redivivus and Ditylenchus dipsaci. Protein determinations are corrected for dilutions in homogenate preparation. Data are presented as the average of two measurements shown in parenthesis..........................................................................................................28 Table 2. Esterase activity in homogenates of Panagrellus redivivus and Ditylenchus dipsaci measured as rate of substrate hydrolysis per mg of protein in thirty minutes .....................................................................................................................28 Table 3. Esterase activity in homogenates of Panagrellus redivivus and Ditylenchus dipsaci after storage at – 18oC for 0 to 14 days.............................................33 Table 4. The influence of time on phorate inhibition of esterase activity in homogenages of Panagrellus redivivus. Substrate hydrolysis rates were measured after 0 – 30 minutes preassay incubation of a 5 x 10-4 M phorate treatment and untreated homogenates.......................................................................................................35 Table 5. Phorate, paraoxon, and eserine inhibition of non-specific esterase activyt in Panagrellus redivivus. Treated and control homogenates were preincubated 30 minutes at 28oC prior to assay of beta-naphthyl acetate hydrolysis. Each experiment was repeated three times. ...................................................37 Table 6. Phorate, paraoxon, and eserine inhibition of cholinesterase acticity in Panagrellus redivivus. Treated and control homogenates were preincubated 30 minutes at 28oC prior to assay of acetyl choline chloride hydrolysis. Each experiment was repeated 2 times. ......................................................................................39 Table 7. Phorate, paraoxon, and eserine inhibition of non-specific esterase activity in Ditylenchus dipsaci. Treated and control homogenates were preincubated 30 min at 28oC prior to assay of beta-naphthyl acetate hydrolysis. Each experiment was repeated 3 times. .............................................................................43 Table 8. The interaction of chlordane, DDT, dieldrin and lindane with the antiesterase activity of phorate. Homogenates of Panagrellus redivivus and Ditylenchus dipsaci were treated
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