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1.
Dimethoate [O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithioate] was oxidatively metabolized by primary human embryonic lung cells in culture. Over 95% of the recovered radioactivity after incubation with 14C-labeled dimethoate resulted from oxidative metabolites, with the remainder being water soluble. Thus, oxidative metabolism of dimethoate predominated over hydrolytic metabolism in the cell culture system, in contrast to the whole rat where the opposite is true. The sequence of reactions was similar to that found in rats. Dimethoate was desulfurated to yield dimethoxon and both compounds were N-demethylated. Metabolism of dimethoate in mouse fibroblast L-929 cell cultures revealed up to 35% of dimethoate carboxylic acid as the only compound other than dimethoate present.  相似文献   

2.
The prolonged use of dimethoate, introduced into Denmark to control houseflies (Musca domestica L.) that had become resistant to parathion and diazinon, resulted ultimately in dimethoate resistance. Selection with dimethoate led to the disappearance of the hydrolytic phosphatase, a major mechanism of resistance to parathion and diazinon, and its replacement by the acetylcholinesterase AChER with somewhat decreased sensitivity to inhibition by organophosphorus (OP) insecticides. The hydrolytic phosphatase probably disappeared because low substrate turn-over made it ineffective against dimethoxon (O, O-dimethyl S-methylcarbamoylmethyl phosphorothioate, also known as omethoate). which accumulates at higher concentrations than paraoxon (diethyl4-nitrophenyl phosphate) in the haemolymph. Dimethoate selected AChER preferentially because it improved the chances of houseflies surviving against the relatively poor AChE inhibitor dimethoxon, whereas its relatively small insensitivity to OP insecticides, unimportant against good inhibitors such as paraoxon, prevented its selection by parathion.  相似文献   

3.
0.02% a.i. dicrotophos and dimethoate, 0.025% a.i. demeton-S-methyl, thiometon, chlorfenvinphos and methomyl, and 0.03% a.i. phosphamidon were evaluated in the field for control of aphids (Myzus persicae Sulzer) infesting tobacco. All the insecticides were effective but chlorfenvinphos and methomyl were inferior to the rest. 0.03% and 0.06% a.i. endosulfan and trichlorfon, 0.05% and 0.1% a.i. carbaryl, and 0.025% and 0.05% a.i. methomyl were evaluated in the field for control of caterpillars ofSpodoptera litura (F.) defoliating tobacco. Nearly all the insecticides were effective and carbaryl and trichlorfon gave satisfactory control even at the lower concentrations tested.  相似文献   

4.
Orally administered [1-14C]ethyl paraoxon, O,O-diethyl-O-p-nitrophenyl phosphate, is readily absorbed from the gastrointestinal tract of male albino rats. Radioactivity is essentially eliminated in 72 hr by excretion into urine and feces and by expiration as 14CO2. Compounds with radioactivity in the urine are tentatively identified as diethyl phosphoric acid, desethyl paraoxon, ethanol, metabolites conjugated with amino acids, and paraoxon; the first compound is the predominant radioactive metabolite. Intraperitoneally injected phenobarbital, DDT, dieldrin, and endrin are inducers of microsomal enzymes that degrade paraoxon. The aryl phosphate-cleaving activity in vitro is not dependent on the addition of NADPH. O-Dealkylation of paraoxon is catalyzed by microsomal enzymes that require NADPH and oxygen and are inhibited by carbon monoxide. Microsomal enzymes from rats pretreated with enzyme inducers give an increased rate of O-dealkylation of paraoxon. Reduced glutathione has little or no effect on paraoxon degradation by either microsomal or soluble enzymes. Actinomycin D inhibits O-dealkylation of paraoxon in vivo, as indicated by reduction of 14CO2 formation, and in vitro, as indicated by decreased activity of microsomal O-dealkylase. The role of microsomal mixed-function oxidases and NADPH-dependent O-dealkylase in the metabolism of organophosphorus insecticides is discussed.  相似文献   

5.
p,p′-DDT was converted to DDD, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, by unheated 12,000g supernate supplemented with NADPH, made from liver of rat, mouse, hamster, quail, chicken and pigeon. The additional presence of exogenous riboflavin did not augment reduction. If, however, riboflavin was added to unheated microsomes supplemented with NADPH or NADH the rate of reduction was more than doubled.Heated 12,000g supernate, unsupplemented or containing only exogenous riboflavin, did not reduce DDT. When NAD(P)H was present, big species differences in activity occurred, the pigeon and cockerel scarcely reducing any DDT in 2 hr, the Wistar rat supernate being most active. Addition to heated 12,000g supernate of 30 μg riboflavin as well as NAD(P)H resulted in increased reductive activity for all six species. The species difference in effect of exogenous riboflavin between the pigeon and rat was also observed using four DDT analogs as substrates. A sex-related difference in activity of preheated, supplemented 12,000g supernate from livers of the chicken and Norwegian hooded rat was not found when unheated preparations were used. In contrast to the activity possessed by preheated 12,000g supernate of rat liver supplemented with NAD(P)H, similarly supplemented preheated microsomes did not reduce DDT. On adding riboflavin as well as NAD(P)H, however, preheated hepatic microsomes of both pigeon and rat produced DDD, and this activity was further increased by addition of unheated microsomal (105,000g) supernate. The biocatalytic system functioning in preheated preparations appears to need at least one component of heated microsomes, NAD(P)H and one or more water-soluble components.  相似文献   

6.
The effect of phenobarbital and certain pesticides on glutathione S-transferase activity was investigated. The maximum amount of enzyme induction occurred 96 hr after phenobarbital treatment. Chlorinated hydrocarbons were more effective inducers than the other pesticides evaluated. Phenobarbital treatment did not alter the apparent Km value but altered the Vmax value of glutathione S-transferase to 3,4-dichloronitrobenzene. The amount of reduced glutathione was not increased by phenobarbital treatment. Pretreatment of house flies with phenobarbital provides some protection against methyl parathion, methyl paraoxon, azinphosmethyl, and methidathion toxicity.  相似文献   

7.
The in vitro metabolism of EPN (O-ethyl O-p-nitrophenyl phenylphosphonothionate) and EPNO (O-ethyl O-p-nitrophenyl phenylphosphonate) in mouse liver was studied. EPNO was metabolized faster than EPN, and the highest metabolic activity was found in the 10,000g supernatant in the presence of both NADPH and glutathione. Liver microsomes in the presence of NADPH metabolize EPN to its oxygen analog, EPNO and p-nitrophenol. With the 100,000g supernatant only slight metabolism of EPN occurred in the presence of GSH. Metabolism of EPNO by liver microsomes increased upon the addition of NADPH. p-Nitrophenol was the only metabolite isolated in the presence of microsomes, whereas, with the addition of NADPH, both p-nitrophenol and desethyl EPNO were formed. Quantitative studies showed that there was little, if any, oxidative dearylation of EPNO by liver microsomes. The 100,000g supernatant was found to actively degrade EPNO, and this increased upon addition of glutathione. The initial rate of p-nitrophenol formation as a result of incubation of EPN and EPNO with liver microsomes was found to be higher with EPN than EPNO.  相似文献   

8.
Cytochrome P-450, A- and B-esterase, amidase, and glutathione S-aryl transferase were assayed in the postmitochondrial centrifugal fraction, microsomes, and supernatant of rat liver, lungs, kidneys, and testes. Liver microsomes contained the highest P-450 levels and A-esterase activity. B-esterase activity was more generally distributed and higher in the microsomal tissue fractions. Microsomal amidase activity was highest in rat lung and lowest in the liver (per mg protein). Glutathione S-aryl transferase activity was highest in the liver. The in vitro metabolism of carbaryl, phosphamidon, and chlorotoluron by the various centrifugal fractions revealed many differences. Carbaryl metabolism was greater in the liver microsomal fractions than in any other preparation. 1-Naphthol was the major metabolite in all tissue fractions. Although very little metabolism of phosphamidon occurred in the rat, metabolism in the rat liver postmitochondrial fraction was slightly higher with respect to the production of metabolites than in the supernatant and microsomes combined. Chlorotoluron was not metabolized by any of the tissue fractions of the rat. At least a low level of activity toward some compounds was observed in all tissues, but this study confirmed that the liver was the most active metabolizing tissue as well as having the highest levels of enzymatic activity usually associated with pesticide metabolism.  相似文献   

9.
The cecropia juvenile hormone and three of its analogs were compared as inducers of microsomal epoxidase, O-demethylase, and DDT dehydrochlorinase in the housefly, Musca domestica L. The compounds were the cecropia juvenile hormone, methoprene, hydroprene, 6,7-epoxy-3,7-diethyl-1-[3,4-(methylenedioxy)phenoxy]-2-octene, and piperonyl butoxide, a well known insecticide synergist. The compounds were administered by feeding at levels up to 1% in the diet for 3 days to 1-day-old female adults. Enzymes were then prepared and assayed for their activity using heptachlor, p-nitroanisole, and DDT as substrates.There was approximately a twofold increase in the microsomal oxidases and a 50% increase in DDT dehydrochlorinase after the treatment with the cecropia juvenile hormone, while methoprene had some activity as an inducer of the epoxidase (30% increase) but no activity in the case of the O-demethylase or the dehydrochlorinase. Hydroprene had no effect on any of the enzyme systems, while 6,7-epoxy-3,7-diethyl-1-[3,4-(methylenedioxy)phenoxy]-2-octene was an inhibitor of the two microsomal oxidases. The latter compound and piperonyl butoxide were strong inducers of DDT dehydrochlorinase, causing approximately twofold increases in the activity of this enzyme.There was evidence that the microsomal preparations were able to metabolize and inactivate methoprene and hydroprene, the action being oxidative in the case of methoprene and both oxidative and hydrolytic in the case of hydroprene. The oxidative metabolism of the two juvenile hormone analogs by the microsomal preparations was inducible by the cecropia juvenile hormone and by phenobarbital and dieldrin.  相似文献   

10.
In the Japanese quail, cytochrome P-450, A- and B-esterase, amidase, and glutathione S-aryl transferase were assayed in postmitochondrial centrifugal fractions, in microsomes, and supernatant fractions of liver, lungs, kidneys, and testes. Liver microsomes contained the highest A-esterase activity and P-450 levels. B-esterase was more generally distributed and higher in the microsomal tissue fractions. Microsomal amidase activity was highest in quail lung and kidney, and lowest in the liver (per mg protein). Very little difference in glutathione S-aryl transferase activity was noted among the tissues assayed. In vitro metabolism of carbaryl, phosphamidon, and chlorotoluron by the various centrifugal fractions revealed that the production of 1-naphthyl-N-hydroxymethylcarbamate and 1-naphthol, the major metabolites, was greatest in the postmitochondrial fraction of the liver. The major carbaryl metabolite in all other quail tissue fractions was 1-naphthol. Phosphamidon metabolism in postmitochondrial preparations of quail liver was higher than in the supernatant and microsomes. Chlorotoluron metabolism occurred only in the postmitochondrial fractions of quail liver. The major products were the oxidative metabolites, N-(3-chloro-4-methylphenyl)-N′-methylurea and N-(3-chloro-4-hydroxymethylphenyl)-N′-methylurea.  相似文献   

11.
[14C]-Dieldrin was detected in the hemolymph of adult male Periplaneta americana and P. brunnea 2.5 hr after an acetone solution of radiodieldrin (RD) was applied to the pronotum. Sephadex thin-layer gel filtration (TLG) of cell-free hemolymph (HL) from cockroaches to which RD was applied, and TLG of HL to which RD was added directly, indicated that dieldrin binds to a protein (s) of ca. 18,900 mol wt and two groups of proteins of mol wt ≥ 160,000. The capacity of Periplaneta HL for RD at 22°C was to at least 57 μM, but the highest concentration of RD detected in HL after topical application was 29.9 μM. The hemocytes contained about 37% of the dieldrin in whole cockroach hemolymph. When isolated cockroach legs were perfused with HL containing protein-bound RD, autoradiography of the dissected legs revealed 14C counts in the tissues. These findings are consistent with the translocation of topical dieldrin by hemolymph, but do not eliminate the possibility of translocation via the tracheal system.  相似文献   

12.
The in vivo formation of deethylation and hydrolytic products of paraoxon degradation after parathion or paraoxon administration was nearly equal in control male rats, and the relative abundance of metabolites was not appreciably altered by pretreatment of rats with enzymeinducing agents. However, pretreatment with inducers dramatically increased the oxidative paraoxon O-deethylase of male rat liver while having little effect on hydrolytic enzymes. Prior to induction, the hepatic O-deethylase activity was greatly inferior to the various hydrolytic enzymes, but nearly equal levels of both enzyme systems were found after induction. These results indicate that a large portion of the hepatic hydrolases detected in vitro is not active in vivo. It also appears that the majority of the induced hepatic deethylase was not involved in vivo at the dosage levels employed. The in vivo metabolism of monoethyl paraoxon was also demonstrated. The predominant metabolite of ethyl-[1-14C]monoethyl paraoxon is 14CO2, while phenyl-[1-14C]monoethyl paraoxon yielded 4-nitro[1-14C]phenol. Paraoxon deethylation was also shown to be an important detoxication mechanism in female rats and male mice and must be considered in interpreting the toxicological properties of parathion and paraoxon.  相似文献   

13.
Development and phenobarbital (PB) induction of microsomal cytochrome P-450, cytochrome P-450 reductase, two epoxidation, and two O-demethylation activities were examined in chronologically timed populations of insecticide-susceptible (NAIDM) and -resistant (Rutgers) house flies. Measurements of these enzymes started with the pharate adult stage and ended 5 days following eclosion. Untreated insects of both strains had comparable reductase levels, whereas cytochrome P-450 and associated monooxygenase activities were 1.5-fold or more higher in Rutgers. Maximum induction, as well as toxicity, occurred at a lower PB concentration in NAIDM than Rutgers. The drug caused consistently higher increases in enzymes and activities within 12 hr of starting treatment in both strains. When PB was withdrawn from treated flies (both strains) 48 hr after treatment began, specific activities (product min?1 mg protein?1) in all enzymes returned to control values in 24 hr while metabolic capacity (product min?1 insect?1) achieved control values within 48 hr. The changes in turnover numbers (pmol product min?1 pmol P-450?1), in conjunction with the differences in the monooxygenation of the four substrates, suggest that PB treatment induced both a quantitative and qualitative change in NAIDM monooxygenation but only a quantitative change in Rutgers monooxygenation.  相似文献   

14.
The polysubstrate monooxygenases (PSMO or cytochrome P-450) of house fly larvae were studied at the mature larval or “clear gut” stage. Fat body and gut tissues were most efficient in the conversion of aldrin to dieldrin. Microsomal fractions of larval homogenates had the highest PSMO activities, with lower PSMO activities also found associated with mitochondrial fractions. Microsomes from Rutgers (resistant) larvae had higher levels of NADPH:cytochrome c reductase (2×), cytochrome P-450 (2×), aldrin (4×), and heptachlor (9×) epoxidases than microsomes from CSMA (susceptible) larvae. Cytochrome P-450 of Rutgers larvae had an absorption maximum at 449 nm, 2 nm lower than the cytochrome P-450 of CSMA larvae. n-Octylamine spectra showed that the level of high-spin cytochrome P-450 was higher in Rutgers larvae. NADPH:cytochrome c reductase, cytochrome P-450, and aldrin epoxidase were induced by phenobarbital, and Rutgers larvae were shown to be more sensitive to this inducer than CSMA larvae. Induction of larval PSMO by phenobarbital did not affect the expression or the inducibility of PSMO in adults.  相似文献   

15.
The rapid effects of the thiocarbamate herbicide S-ethyl dipropyl thiocarbamate (EPTC) and the herbicide protectant N,N-diallyl-2,2-dichloroacetamide (DDCA) on macromolecular syntheses and glutathione (GSH) levels in maize cell cultures were studied to determine whether stimulation of GSH could be the primary mechanism of action of DDCA. EPTC (0.5 and 1 mM) reduced incorporation of radioactive precursors within 1 hr after treatment, and affected incorporation of [3H]acetate into lipids more than incorporation of [3H]adenosine into acid-precipitable nucleic acids, or [14C]protein hydrolysate into protein. [14C]EPTC was rapidly biotransformed within 8 hr by maize cell suspensions. Measureable decreases in GSH levels following treatment with 1 mM EPTC occurred after 15 hr. DDCA stimulated incorporation of [3H]acetate into lipids within 4 hr but did not affect incorporation of [14C]protein hydrolysate into protein or [3H]adenosine incorporation into nucleic acids. Measureable increases in GSH following DDCA treatment began after 12 hr. Treatment with EPTC and DDCA in combination inhibited incorporation of [3H]acetate into lipids less than EPTC given alone. Increases in GSH levels could be observed following pretreatments with glutathione precursors, but no protectant activity could be detected, in contrast to treatments with DDCA. It is suggested that DDCA has an initial rapid effect on lipid metabolism followed by a slower effect involving increases in cellular GSH.  相似文献   

16.
In apterous adults of the spirea aphid, Aphis citricola van der Goot, the optimum conditions for determining acetylcholinesterase (AChE) activity consist of reaction mixture of 0.1 M phosphate buffer (pH 7.5), 10?3M acetylthiocholine (ASCh), and enzyme extract equivalent to 80 ± 3 μg protein incubated for 15 min at 30°C. The Km value for ASCh (6.7 × 10?5M) was much lower than that of butyrylthiocholine (BuSCh) (1.25 × 10?2M). The enzyme activity was almost completely inhibited by 10?6M paraoxon or 10?5M eserine and was 84% inhibited by 10?5M BW284C51 (a specific AChE inhibitor). DTNB was found to inhibit the enzyme activity and was therefore added at the end of the reaction. AChE activity of A. citricola was inhibited in vitro and in vivo by dimethoxon > dimethoate, and aldicarb sulfoxide > aldicarb > aldicarb sulfone. The in vivo effect correlates well with the toxicity level of the various toxicants. A neurotoxicity index which combines both mortality and in vivo inhibition of the aphid AChE activity is suggested as a measure for determining the toxicity of organophosphorus and carbamate compounds toward aphids.  相似文献   

17.
The exposure of bluegill fish to 50 parts per billion [14C]dieldrin in a static system resulted in the absorption of 73.00% of the radioactivity in 48 hr. Following transfer of the fish to clean water, only 16.20% of the absorbed radiolabel was eliminated in 23 days. Out of the 93.65% of the absorbed radioactivity recovered, 9 radioactive spots were isolated which included unchanged dieldrin (74.39%), pentachloroketone (8.17%), and aldrin-trans-diol (8.04%) as major metabolites.  相似文献   

18.
Microsome fractions were prepared from liver homogenates of control rats and rats treated with DDT. The increased incorporation of [14C]phenylalanyl-tRNA into peptide when microsomes or ribosomes derived from DDT-treated rats were incubated with supernatant was due to factors in addition to increased endogenous mRNA. These factors were not related to the decreased activity of ribonuclease and increased activity of ribonuclease inhibitor, nor to the GTP and thiol sensitive inhibitor. The factors were partly removed from microsomes and completely removed from ribosomes by procedures using a 0.5 M KCl wash. Treatment of rats with polychlorinated biphenyls gave results similar to DDT. The 0.5 M KCl wash fraction from the control preparations contained factors inhibitory to protein synthesis in contrast to the wash fraction from the DDT preparations.  相似文献   

19.
Only about 60% of the total relative gravitational force conventionally used to sediment microsomes is needed to prepare highly active microsomes from the midgut tissues of an insect larva. A rapid preliminary centrifugation for 2 min at 39,000gmax effectively removed contaminating microorganisms, tissue debris, nuclei, and mitochondria. The supernatant was recentrifuged for 20 min to 210,000g to sediment the microsomes. There were no losses of microsomal oxidase activities or degradation of cytochrome P-450 to the inactive form (P-420) resulting from the application of the higher gravitational force. Incorporation of 1 mM EDTA in the buffer and washing the microsomes resulted in an improved yield of the cytochrome compared to that in microsomes prepared in sucrose. Yields of microsomal protein, cytochrome P-450, and NADPH-cytochrome c reductase in the rapidly isolated microsomes were as good as those in conventionally prepared microsomes. The apparent kinetic characteristics of several microsomal oxidation activities and optical difference spectra of Types 1 and 2 ligands were identical in the rapidly and conventionally prepared microsomes. The morphological appearance of the microsomes was examined by electron microscopy. Microsomal pellets prepared by either method were indistinguishable. The rapid procedure saves significant time in microsome preparation and yields microsomal oxidase activities as good or slightly better than those prepared by usual centrifuged procedures.  相似文献   

20.
The responses of brain and plasma cholinesterase (ChE) activities were examined in mallard ducks, bobwhite quail, barn owls, starlings, and common grackles given oral doses of dicrotophos, an organophosphorus insecticide. Up to an eightfold difference in response of brain ChE activity to dicrotophos was found among these species. Brain ChE activity recovered to within 2 SD of normal within 26 days after being depressed 55 to 64%. Recovery of brain ChE activity was similar among species and followed the model Y = a + b (log10X).  相似文献   

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