-
Molecular Medicine (Cambridge, Mass.) 2007Cancer of the breast is the most common form of malignant disease occurring among women of the western world and environmental substances seem to be involved in the...
Cancer of the breast is the most common form of malignant disease occurring among women of the western world and environmental substances seem to be involved in the etiology of this disease. Many studies have found an association between human cancer and exposure to agricultural pesticides and among them parathion, the organophosphorous pesticide used in agriculture to control mosquito plagues. The association between breast cancer and prolonged exposure to estrogens suggests that this hormone also may have a role in such process. However, the causative factors for breast carcinogenesis remain an enigma. The objective of this study was to determine the effects of 17beta-estradiol (E2) and parathion on cell transformation of human breast epithelial cells in vitro. The results of this study showed that parathion alone and in combination with E2 induced malignant transformation of an immortalized human breast epithelial cell line, MCF-10F, and the malignant feature was confirmed by anchorage independency and invasive capabilities. Parathion alone efficiently elevated the expression of EGFR, c-Kit, Trio, Rac 3, Rho-A, and mutant p53 proteins. Analysis of gene expression using commercially available human cell cycle array revealed transcriptional alterations in 22 out of a total of 96 genes. Among them, nine genes involved in the regulation of cell cycle were altered. These included cyclins (A1, A2, C, G1, G2, and H), cyclin-dependent kinases (CDKs), and minichromosome maintenance deficient (MCM). Results suggest that parathion has the potency to cause malignant transformation of breast epithelial cells through modulation of expression of cell cycle regulated genes.
Topics: Breast; Cells, Cultured; Epithelial Cells; Estradiol; Gene Expression Profiling; Gene Expression Regulation; Humans; Parathion; Proteins
PubMed: 17622325
DOI: 10.2119/2006–00087.Calaf -
Ecotoxicology and Environmental Safety Jun 2001The in vivo effects of parathion and endosulfan on the isopod Porcellio dilatatus were investigated. Feeding parameters (food consumption and assimilation rates),...
The in vivo effects of parathion and endosulfan on the isopod Porcellio dilatatus were investigated. Feeding parameters (food consumption and assimilation rates), growth, and energy reserves (glycogen, lipid, and protein contents) of pesticide-exposed isopods were compared with those of control animals. Isopods were exposed to a wide range of concentrations of parathion or endosulfan (0.1, 1, 10, 25, 50, 100, 250, and 500 microg/g of food) for 21 days. The route of uptake of the pesticides was through the diet (alder leaves). Results revealed that parathion induces a significant depression of glycogen, lipid, and protein contents. However, no significant effect was observed on either feeding parameters or growth. Animals fed endosulfan-contaminated food had smaller amounts of glycogen and lipid than control animals, while protein levels were similar in all treatments. Endosulfan also induced a significant decrease in food consumption and assimilation rates at the highest concentrations tested. Growth rate was also significantly affected by endosulfan. These results suggest that the isopod P. dilatatus is a suitable species for use in toxicity tests and that energy reserves could be used as effect criteria in both laboratory and field studies.
Topics: Animals; Crustacea; Diet; Dose-Response Relationship, Drug; Eating; Endosulfan; Energy Metabolism; Glycogen; Insecticides; Lipid Metabolism; Longevity; Parathion; Proteins; Toxicity Tests
PubMed: 11386726
DOI: 10.1006/eesa.2001.2045 -
Ultrasonics Sonochemistry Jun 2010Ultrasonic degradation of parathion has been investigated in this study. At a neutral condition, 99.7% of 2.9 microM parathion could be decomposed within 30 min under...
Ultrasonic degradation of parathion has been investigated in this study. At a neutral condition, 99.7% of 2.9 microM parathion could be decomposed within 30 min under 600 kHz ultrasonic irradiation at ultrasonic intensity of 0.69 W/cm(2). The degradation rate increased proportionally with the increasing ultrasonic intensity from 0.10 to 0.69 W/cm(2). The parathion degradation was enhanced in the presence of dissolved oxygen due to formation of more ()OH, but was inhibited in the presence of nitrogen gas owning to the free radical scavenging effect in vapor phase within the cavitational bubbles. CO(3)(2-), HCO(3)(-), and Cl(-) exhibited the inhibiting effects on parathion degradation, and their inhibition degrees followed the order of CO(3)(2-)>HCO(3)(-)>Cl(-). But Br(-) had a promoting effect on parathion degradation, and the effect increased with the increasing Br(-) level. Moreover, both the hydrophobic and hydrophilic natural organic matters (NOM) could slow the parathion degradation, but the inhibiting effect caused by hydrophobic component was greater, especially the strongly hydrophobic NOM. The three reaction pathways of parathion sonolysis were proposed, including formation of paraoxon, formation of 4-nitrophenol, and unknown species products. The kinetics tests showed that anyone of these pathways could not be overlooked, and the fractions of the parathion decomposed in the three pathways were 28.19%, 32.92% and 38.89%, respectively. In addition, 66.61% of paraoxon produced was degraded into 4-nitrophenol. Finally, kinetics models were established to adequately predict the concentrations of parathion, paraoxon and 4-nitrophenol as a function of time.
Topics: Parathion; Sonication; Water; Water Pollutants; Water Purification
PubMed: 20303819
DOI: 10.1016/j.ultsonch.2010.01.016 -
Frontiers in Microbiology 2022Organophosphate compounds are widely used in pesticides to control weeds, crop diseases, and insect pests. Unfortunately, these synthetic compounds are hazardous and...
Organophosphate compounds are widely used in pesticides to control weeds, crop diseases, and insect pests. Unfortunately, these synthetic compounds are hazardous and toxic to all types of living organisms. In the present work, was bioengineered to achieve methyl parathion (MP) degradation via the introduction of six synthetic genes, namely, , , , , , and , to obtain a new transformant, BL-MP. MP and its subsequent decomposition intermediates were completely degraded by this transformant to enter the metabolites of multiple anabolic pathways. The MP-degraded strain created in this study may be a promising candidate for the bioremediation of MP and potential toxic intermediates.
PubMed: 35222319
DOI: 10.3389/fmicb.2022.679126 -
Biochimica Et Biophysica Acta Jan 2013Phosphotriesters are one class of highly toxic synthetic compounds known as organophosphates. Wide spread usage of organophosphates as insecticides as well as nerve... (Review)
Review
Phosphotriesters are one class of highly toxic synthetic compounds known as organophosphates. Wide spread usage of organophosphates as insecticides as well as nerve agents has lead to numerous efforts to identify enzymes capable of detoxifying them. A wide array of enzymes has been found to have phosphotriesterase activity including phosphotriesterase (PTE), methyl parathion hydrolase (MPH), organophosphorus acid anhydrolase (OPAA), diisopropylfluorophosphatase (DFP), and paraoxonase 1 (PON1). These enzymes differ widely in protein sequence and three-dimensional structure, as well as in catalytic mechanism, but they also share several common features. All of the enzymes identified as phosphotriesterases are metal-dependent hydrolases that contain a hydrophobic active site with three discrete binding pockets to accommodate the substrate ester groups. Activation of the substrate phosphorus center is achieved by a direct interaction between the phosphoryl oxygen and a divalent metal in the active site. The mechanistic details of the hydrolytic reaction differ among the various enzymes with both direct attack of a hydroxide as well as covalent catalysis being found. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.
Topics: Animals; Aryldialkylphosphatase; Binding Sites; Catalysis; Catalytic Domain; Cations, Divalent; Humans; Metals; Models, Chemical
PubMed: 22561533
DOI: 10.1016/j.bbapap.2012.04.004 -
Applied and Environmental Microbiology Oct 2021-Nitrophenol (PNP) is a hydrolytic product of organophosphate insecticides, such as parathion and methylparathion, in soil. Aerobic microbial degradation of PNP has been...
-Nitrophenol (PNP) is a hydrolytic product of organophosphate insecticides, such as parathion and methylparathion, in soil. Aerobic microbial degradation of PNP has been classically shown to proceed via the "hydroquinone (HQ) pathway" in Gram-negative degraders, whereas it proceeds via the "benzenetriol (BT) pathway" in Gram-positive ones. The "HQ pathway" is initiated by a single-component PNP 4-monooxygenase and the "BT pathway" by a two-component PNP 2-monooxygenase. Their regioselectivity intrigued us enough to investigate their catalytic difference through structural study. PnpA1 is the oxygenase component of the two-component PNP 2-monooxygenase from Gram-positive Rhodococcus imtechensis strain RKJ300. It also catalyzes the hydroxylation of 4-nitrocatechol (4NC) and 2-chloro-4-nitrophenol (2C4NP). However, the mechanisms are unknown. Here, PnpA1 was structurally determined to be a member of the group D flavin-dependent monooxygenases with an acyl coenzyme A (acyl-CoA) dehydrogenase fold. The crystal structure and site-directed mutagenesis underlined the direct involvement of Arg100 and His293 in catalysis. The bulky side chain of Val292 was proposed to push the substrate toward flavin adenine dinucleotide (FAD), hence positioning the substrate properly. An N450A variant was found with improved activity for 4NC and 2C4NP-probably because of the reduced steric hindrance. PnpA1 shows an obvious difference in substrate selectivity with its close homologues TcpA and TftD, which may be caused by the unique Thr296 and a different conformation in the loop from positions 449 to 454 (loop 449-454). Above all, our study allows structural comparison between the two types of PNP monooxygenases. An explanation that accounts for their regioselectivity was proposed: the different PNP binding manners determine their choice of - or -hydroxylation on PNP. Single-component PNP monoxygenases hydroxylate PNP at the 4 position, while two-component ones do so at the 2 position. However, their catalytic and structural differences remain elusive. The structure of single-component PNP 4-monooxygenase has previously been determined. In this study, to illustrate their catalytic difference, we resolved the crystal structure of PnpA1, a typical two-component PNP 2-monooxygenase. The roles of several key amino acid residues in substrate binding and catalysis were revealed, and a variant with improved activities toward 4NC and 2C4NP was obtained. Moreover, through comparison of the two types of PNP monooxygenases, a hypothesis was proposed to account for their catalytic difference, which gives us a better understanding of these two similar reactions at the molecular level. In addition, these results will also be of further aid in rational design of enzymes in bioremediation and biosynthesis.
Topics: Bacterial Proteins; Catalysis; Mixed Function Oxygenases; Nitrophenols; Rhodococcus
PubMed: 34469195
DOI: 10.1128/AEM.01171-21 -
Environment International Sep 2018Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
BACKGROUND
Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
OBJECTIVE
We assessed associations between pesticide use and other farm exposures and incident hypothyroidism and hyperthyroidism in female spouses of farmers in the Agricultural Health Study (AHS).
METHODS
We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals for risk of thyroid disease in 24,092 spouses who completed at least one follow-up questionnaire.
RESULTS
We identified 1627 hypothyroid and 531 hyperthyroid cases over 20 years of follow-up. The fungicides benomyl, maneb/mancozeb, and metalaxyl, the herbicide pendimethalin, and among those over 60 years of age the insecticides parathion and permethrin (applied to crops) were associated with elevated hypothyroidism risk, with HR ranging from 1.56-2.44. Conversely, the insecticide phorate, and the herbicides imazethapyr and metolachlor were associated with decreased risk (HR ranging 0.63-0.73), as were long-term farm residence and other farm-related activities (HR ranging 0.69-0.84). For hyperthyroidism, the insecticide diazinon, the fungicides maneb/mancozeb, and the herbicide metolachlor were associated with increased risk (HR ranging 1.35-2.01) and the herbicide trifluralin with decreased risk (HR: 0.57).
CONCLUSIONS
Several individual pesticides were associated with increased risk of hypothyroidism and hyperthyroidism, although some pesticides were associated with decreased risk. Some of the findings, specifically associations with fungicides, are consistent with results from an earlier analysis of prevalent diseases in AHS spouses.
Topics: Female; Follow-Up Studies; Humans; Male; Occupational Exposure; Pesticides; Spouses; Surveys and Questionnaires; Thyroid Diseases
PubMed: 29908479
DOI: 10.1016/j.envint.2018.05.041 -
RSC Advances Jun 2022To achieve rapid and convenient on-site pretreatment and determination of parathion-methyl, a density-adjusted liquid-phase microextraction with smartphone digital image...
Density-adjusted liquid-phase microextraction with smartphone digital image colorimetry to determine parathion-methyl in water, fruit juice, vinegar, and fermented liquor.
To achieve rapid and convenient on-site pretreatment and determination of parathion-methyl, a density-adjusted liquid-phase microextraction with smartphone digital image colorimetry was established to detect parathion-methyl in food samples. In this study, the environmentally friendly biomass-derived solvent guaiacol was used as the extractant. Salt and water, as density regulators, realized the two movements (floating-sinking) of the extractant and full contact between the extractant and the sample solution to establish an environmentally friendly, fast, and efficient pretreatment method. Under strong alkaline conditions, parathion-methyl generated a yellow product; then, a smartphone was used to obtain the image of the yellow product for intensity analysis. Parathion-methyl has a good linear relationship in the range of 0.01-1 mg L, and the limits of detection and quantification are 0.003 and 0.01 mg L, respectively. This method has been successfully applied to the determination of parathion-methyl in spiked water, fruit juice, vinegar, and fermented liquor with a recovery of 91.6-106.5% and a relative standard deviation of 0.6-6.0%. The established density-adjusted liquid phase microextraction with smartphone digital image colorimetry is rapid, convenient, and environmentally friendly for the determination of parathion-methyl in food samples.
PubMed: 35800312
DOI: 10.1039/d2ra02760g -
Toxicology Jul 2011Organophosphorus pesticides (OPs) remain a potential concern to human health because of their continuing use worldwide. Phosphororthioate OPs like chlorpyrifos and...
Organophosphorus pesticides (OPs) remain a potential concern to human health because of their continuing use worldwide. Phosphororthioate OPs like chlorpyrifos and parathion are directly activated and detoxified by various cytochrome P450s (CYPs), with the primary CYPs involved being CYP2B6 and CYP2C19. The goal of the current study was to convert a previously reported human pharmacokinetic and pharmacodynamic (PBPK/PD) model for chlorpyrifos, that used chlorpyrifos metabolism parameters from rat liver, into a human CYP based/age-specific model using recombinant human CYP kinetic parameters (V(max), K(m)), hepatic CYP content and plasma binding measurements to estimate new values for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and to use the model as a template for the development of a comparable parathion PBPK/PD model. The human CYP based/age-specific PBPK/PD models were used to simulate single oral exposures of adults (19 year old) and infants (1 year) to chlorpyrifos (10,000, 1000 and 100 μg/kg) or parathion (100, 25 and 5 μg/kg). Model simulations showed that there is an age dependency in the amount of blood cholinesterase inhibition observed, however additional age-dependent data are needed to further optimize age-specific human PBPK/PD modeling for these OP compounds. PBPK/PD model simulations estimated that a 4-fold increase or decrease in relative CYP2B6 and CYP2C19 content would produce a 9-22% inhibition in blood AChE activity following exposure of an adult to chlorpyrifos (1000 μg/kg). Similar model simulation produced an 18-22% inhibition in blood AChE activity following exposure of an adult to parathion (25 μg/kg). Individuals with greater CYP2B6 content and lower CYP2C19 content were predicted to be most sensitive to both OPs. Changes in hepatic CYP2B6 and CYP2C19 content had more of an influence on cholinesterase inhibition for exposures to chlorpyrifos than parathion, which agrees with previously reported literature that these CYPs are more reaction biased for desulfurization (activation) and dearylation (detoxification) of chlorpyrifos compared to parathion. The data presented here illustrate how PBPK/PD models with human enzyme-specific parameters can assist ongoing risk assessment efforts and aid in the identification of sensitive individuals and populations.
Topics: Age Factors; Animals; Aryl Hydrocarbon Hydroxylases; Chlorpyrifos; Cholinesterase Inhibitors; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Dose-Response Relationship, Drug; Humans; Infant; Insecticides; Liver; Models, Biological; Oxidoreductases, N-Demethylating; Parathion; Rats; Species Specificity; Young Adult
PubMed: 21514354
DOI: 10.1016/j.tox.2011.04.002 -
British Medical Journal Aug 1950
Topics: Humans; Organophosphate Poisoning; Parathion
PubMed: 15434416
DOI: 10.1136/bmj.2.4676.444