Investigating aneuploidy-inducing effect of Nemacur, Rogor, and Dursban in human peripheral blood lymphocyte cultures.

For many years, organophosphate (OP) pesticides have been considered an attractive choice for pest control around the world. Excessive use of OPs is a concerning issue for human health. Although the genotoxic effect of these pesticides has been reported, studies that examined their aneuploidy-inducing effect are limited or absent. Therefore, we sought to investigate the potential of OP pesticides, which are extensively used in the Gaza Strip, to induce aneuploidy in human peripheral blood lymphocyte (PBL) cultures. To achieve this goal, we first assessed the cytotoxic effect of selected concentrations of Nemacur (fenamiphos), Rogor (dimethoate), and Dursban (chlorpyrifos) on human PBL cultures by the MTT assay. Then, fluorescence in situ hybridization (FISH) technique was used to determine the frequency of induced aneuploidy (chromosome loss or gain) in human PBL cultures treated with different concentrations of the three types of OPs. We found that all the OPs treatments used did not show appreciable cytotoxic effects. Increase in frequencies of aneuploidy, chromosome loss, and chromosome gain were observed after each treatment as compared to the results of their respective solvent control cultures, and that increase of aneuploidy was significantly evident at 0.050 mg/ml of Nemacur. It was also noticed that chromosome loss is more frequent than chromosome gain for each concentration of the three types of OPs. While the aneuploidy induction effect of the investigated OPs is not significant (except for the 0.050 mg/ml of Nemacur), these pesticides should be examined further since many people are exposed to them.

Plasma cholinesterase activity is influenced by interactive effect between omethoate exposure and CYP2E1 polymorphisms.

The aim of this study was to explore the association between metabolizing enzyme gene polymorphisms and the decrease in cholinesterase activity induced by omethoate exposure. A total of 180 workers exposed to omethoate over an extended period were recruited along with 115 healthy controls. Cholinesterase activity in whole blood, erythrocyte, and plasma was detected using acetylthiocholine and the dithio-bis-(nitrobenzoic acid) method. Six polymorphic loci of GSTT1(+/-), GSTM1(+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867, and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The gene-environment interactions were analyzed using the generalized linear model method. The cholinesterase activity of erythrocyte and plasma in the exposure group was significantly lower than that in the control group (P < 0.001) in general. The plasma cholinesterase activity in the TT + AT genotype in CYP2E1 rs6413432 was lower than that in the AA genotype in the exposure group (P = 0.016). Interaction between the AA genotype in CYP2E1 rs6413432 and omethoate exposure had a significant effect on plasma cholinesterase activity (P = 0.079). The decrease in plasma cholinesterase activity was associated with interaction between the AA genotypes in rs6413432 and omethoate exposure.

Transcriptomic responses of the clam Meretrix meretrix to the organophosphorus pesticide (dimethoate).

Organophosphorus pesticides (OPs) play a certain role in promoting the development of agriculture and forestry, but they may cause potential harm to aquatic life when entering rivers and polluting water sources. Previous researches have shown that OPs participate in the regulation mechanism of aquatic organisms. Here, our aim is to determine the underlying mechanisms of one OP (dimethoate) at the transcriptional level using the clam Meretrix meretrix. 4119 DEGs were obtained from high-throughput RNA sequencing data. Then, expression profiles of some genes were verified by qPCR, which showed a positive correlation with the RNA sequencing results. 14,481 simple sequence repeats were also identified and could be further used as molecular markers. In addition, some oxidative, immune, and stress-related genes were further discussed and could also be used as biomarkers to indicate the biological response of dimethoate. This study will help to better understand the clam's response mechanism to dimethoate stress.

Transcriptional and physiological effects of the pyrethroid deltamethrin and the organophosphate dimethoate in the brain of honey bees (Apis mellifera).

The pyrethroid deltamethrin and the organophosphate insecticide dimethoate are widely used in agriculture and in urban areas. Both plant protection products (PPPs) unintendedly result in adverse effects in pollinators. Currently, the sublethal effects of both compounds are poorly known, particularly on the molecular and biochemical level. Here we analysed effects of deltamethrin and dimethoate at environmental and sublethal concentrations in honey bee workers by focusing on transcriptional changes of target genes in the brain. In addition, expression of vitellogenin protein and activity of acetylcholinesterase were assessed upon dimethoate exposure to assess physiological effects. Deltamethrin resulted in induction of the cyp9q2 transcript at 0.53 ng/bee, while dimethoate led to induction of vitellogenin on the mRNA and protein level at 2 ng/bee. Transcripts of additional cytochrome P450-dependent monooxygenases (cyps) and genes related to immune system regulation were not differentially expressed upon PPP exposure. Dimethoate but not deltamethrin led to a strong and concentration-related inhibition of the acetylcholinesterase at 2 and 20 ng/bee. Our data demonstrate that deltamethrin and dimethoate exhibit transcriptional effects at environmental concentrations in the brain of honey bees. Dimethoate also strongly affected physiological traits, which may translate to adverse effects in forager bees.

Telomere Length in Workers Was Effected by Omethoate Exposure, GSTM1 Deletion, Interaction Between Smoking and GSTP1 Polymorphisms.

OBJECTIVE: The aim of this study was to explore the association between telomere length and metabolizing enzyme gene polymorphisms and environmental factors in omethoate-exposed workers. METHODS: The gene-environment interactions were analyzed with generalized linear model method. RESULTS: The relative telomere lengths in the individuals with GSTM1-deletion were longer than that in non-deletion genotype in the control group (P = 0.011); the relative telomere lengths with GG+AG genotypes in GSTP1 rs1695 were longer than that of AA genotype in the exposure group (P = 0.039). The interaction between the GG+AG genotypes in GSTP1 rs1695 and smoking exposure had significant effect on telomere length (P < 0.05). CONCLUSIONS: The prolongation of relative telomere length in omethoate-exposed workers was associated with GSTM1-deletion, GG+AG genotypes, and interactions of GG+AG genotypes and smoking factor.

Relationship between alcohol co-ingestion and outcome in profenofos self-poisoning - A prospective case series.

INTRODUCTION: The importance of alcohol co-ingestion for outcome in organophosphorus (OP) insecticide self-poisoning has only been studied for the relatively hydrophilic dimethyl insecticide, dimethoate. We aimed to assess the effect of alcohol in acute poisoning with the lipophilic S-alkyl OP insecticide, profenofos. METHODOLOGY: Demographic and clinical data, including an alcohol history, were prospectively collected from all cases of acute poisoning with agricultural profenofos EC50 presenting to two Sri Lankan hospitals over seven years. RESULTS: Of 1859 patients with acute OP insecticide self-poisoning, 243 (13.1%) reported ingestion of profenofos (male 182/243, 74.9%). Alcohol co-ingestion was reported by 64/243 (26.3%). All patients reporting alcohol co-ingestion were male (64/64 [100%] vs 118/179 [65.9%] not reporting alcohol ingestion, p<0.001). More patients reporting alcohol co-ingestion died (10/64 [15.6%] vs 10/179 [5.6%]; p = 0.013) and required intubation (13/64 [20.3%] vs 16/179 [8.9%], p = 0.016) compared to those who did not co-ingest alcohol. Using multi-logistic regression, controlling for the estimated dose ingested, age (OR 11.1 [2.5 to 48.9] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.1 [1.2 to 7.9]) were independently associated with increased risk of death. Increased risk of intubation was independently associated with age (OR 3.2 [1.6 to 6.6] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.2 [1.6 to 6.4]). CONCLUSION: A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients' self-poisoned with profenofos.

Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or pyrantel.

The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

Dimethoate induces kidney dysfunction, disrupts membrane-bound ATPases and confers cytotoxicity through DNA damage. Protective effects of vitamin E and selenium.

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H2O2 and AOPP levels were higher, while Na(+)-K(+)-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.

Dimethoate induced oxidative damage and histopathological changes in lung of adult rats: modulatory effects of selenium and/or vitamin E.

OBJECTIVE: To determine the efficiency of selenium and/or vitamin E to alleviate lung oxidative damage induced by dimethoate, an organophosphorus compound. METHODS: Adult Wistar rats were exposed during 30 days either to dimethoate (0.2 g/L of drinking water), dimethoate+selenium (0.5 mg/kg of diet), dimethoate+vitamin E (100 mg/kg of diet), or dimethoate+selenium+vitamin E. RESULTS: Exposure to dimethoate caused oxidative stress in lung evidenced by an increase of malondialdehyde, protein carbonyl groups and advanced oxidation protein products. An increase in glutathione peroxidase, superoxide dismutase, catalase and a decrease in acetylcholinesterase and butyrylcholinesterase activities, glutathione, non-protein thiols and vitamins C levels were observed. Histopathological changes in lung tissue were noted as emphysema, hemorrhages and hemosiderin deposits. Co-administration of selenium or vitamin E to the diet of dimethoate treated rats ameliorated the biochemical parameters as well as histological impairments. The joint effect of these elements was more powerful in antagonizing dimethoate-induced lung oxidative damage. CONCLUSION: We concluded that selenium and vitamin E ameliorated the toxic effects of this pesticide in lung tissue suggesting their role as potential antioxidants.

Final results of a phase II trial of preoperative TAC (docetaxel/doxorubicin/cyclophosphamide) in stage III breast cancer.

BACKGROUND: The use of preoperative chemotherapy for breast cancer has been demonstrated to result in similar disease-free survival (DFS) and overall survival (OS) as postoperative adjuvant chemotherapy. Additionally, the rate of pathologic complete response (pCR) in the breast after preoperative chemotherapy has been shown to correlate with survival. The objective of this study was to determine the pCR rate in patients with stage III breast cancer treated with 4 cycles of TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) on day 1 before surgery. PATIENTS AND METHODS: From November 1998 through August 2001, we treated 40 patients (mean age, 47 years) with stage III breast cancer with TAC administered every 3 weeks for 4 cycles. RESULTS: We now report follow-up at 24 months. Responses were seen in 83% of patients, with 25% experiencing a clinical complete response, of which 4 patients (10%) had pCRs. At a follow-up of 2 years, data on DFS and OS are available on 37 patients: 12 patients (38%) had disease progression, and 7 patients (21%) had died. Despite the use of prophylactic ciprofloxacin, some degree of myelosuppression was seen in all patients, with 24 patients (63%) experiencing grade 3/4 neutropenia. CONCLUSION: Based on the pCR rate seen in this trial, docetaxel given concomitantly with AC (doxorubicin/cyclophosphamide) for 4 cycles does not appear to be superior to 4 cycles of AC as preoperative treatment for stage III breast cancer. Based on other trials, longer durations of therapy and/or sequencing of AC and docetaxel may result in a higher pCR rate.

Evaluation of dimethoate-induced implantation delay and nidation by progesterone in albino mice.

We investigated the effect of dimethoate, an organophosphorus insecticide, and progesterone on implantation. Virgin pregnant albino mice received dimethoate orally at a dose of 28 mg/kg body wt/d from days 1 to 7. Laparotomy on day 8 showed no implantation sites. Thereafter, graded doses of progesterone, 4, 9, and 12 mg/kg body wt/d, were administered up to day 15. A group of control mice received a similar quantity of distilled water. Autopsy on day 8 revealed that the control mice were pregnant, with a normal number of implantations and 8.08% pre-implantation loss, whereas treatment with dimethoate for 7 days or with dimethoate for 7 days followed by progesterone for 8 days totally abolished implantation, with a 100% pre-implantation loss. In all treated mice, a significant decrease occurred in body weight gain, as well as in the weight of the ovaries, uterus, and liver when compared with those of control mice. No significant changes were found in other organ weights (kidneys, adrenals, spleen, thymus, or thyroid). The observed effect of dimethoate could be due to an imbalance in the estrogen-progesterone ratio essential for implantation. Alternatively, dimethoate treatment could result in blastotoxicity or have an impact on the hypothalamic-pituitary axis.

[Sanitary characteristics of working conditions in vegetable growing places in the Republic of Tatarstan]. / Gigienicheskaia kharakteristika uslovii truda ovoshchevodov v Respublike Tatarstan.

The paper gives a sanitary characterization of working conditions in closed soil vegetable growing, a branch of agriculture. These conditions are one of the factors predisposing to occupational disease in agricultural workers. Studies in this area may evaluate the risk of occupational diseases.

The garden snail (Helix aspersa) as a bioindicator of organophosphorus exposure: effects of dimethoate on survival, growth, and acetylcholinesterase activity.

The garden snail (Helix aspersa) is currently used as bioindicator of metallic pollution. Our objective was to extend its use to organic chemicals by studying the effects and tissue concentrations of the organophosphorus pesticide dimethoate following dietary uptake. After exposure for four weeks to increasing doses of pesticide in the diet, the median lethal concentration (LC50) was determined to be 3,700 microg/g food. Clinical signs indicated a no-observed-effect concentration of 100 microg/g and a lowest-observed-effect concentration of 250 microg/g. The growth parameters were decreased with increasing exposure to the pesticide. The median effective concentration (EC50), which was evaluated based on both shell diameter and dry weight inhibitions, was 665 and 424 microg/g, respectively, and the EC10 was 180 and 145 microg/g, respectively. Accumulation in the viscera was related to the amount of dimethoate in the food. The bioconcentration factors were low (>6 x 10(-3)). Acetylcholinesterase (AChE) activity was strongly decreased (80% from 250 microg/g). In conclusion, we demonstrated that the species H. aspersa could be a useful sentinel organism for organophosphorus contamination surveys. Among the effects measured, the inhibition of AChE activities and clinical signs were the most sensitive, followed by the growth parameters. These results confirm the suitability of the garden snail for development of sublethal toxicity tests using primary consumers and aboveground organisms.

The effect of dimethoate and cypermethrin on soil-dwelling beetles under semi-field conditions.

The effect of cypermethrin and dimethoate exposure on soil-dwelling beetles, in spring barley at different growth stages, of doses of up to eight times maximum field application rate has been investigated. Doses up to eight times maximum field application rate of cypermethrin did not have any acute effects on larger beetles, such as P. melanarius and C. erratus. Small beetles (A. bilineata, A. dorsale, B. lanpros, B. obtusum) were not harmed by doses up to two times maximum field application rate. T. hypnorum was affected at maximum field rate. Dimethoate at maximum field application rate harmed all species, but in particular the smaller species. When dimethoate was applied in high foliage density fields in the summer, very severe acute effects on spring breeding beetles were found. In the autumn, when only a low crop cover existed, this very high effect was not observed. The severe effect in the summer may be explained by the mode of action of dimethoate on 'old beetles'. The observed high toxic effect of dimethoate on spring breeders in the summer is expected only to have limited effect on the population, because the spring breeders at this time of the year have finished their egg depositing in the soil.