Occupational exposure in spraying and application of non-arsenical insecticides has been classified as a probable human carcinogen. The fundamental molecular mechanisms involved the tumor-related genes. This study aimed to investigate the carcinogenesis effects related to chronic exposure to organophosphate (OP) pesticides in pesticide applicators. This was a cross-sectional study conducted on 27 pesticide applicators and 24 matched controls through the period from June to December 2018. The level of acetylcholinesterase (AChE) was determined and the effects of OPs exposure on messenger RNA (mRNA) expression of the DNA-damage responsive genes P53, P21, GADD45a, and MDM2 were determined using real-time quantitative polymerase chain reaction. A significant reduction of serum AChE enzyme activities was observed in chronically exposed subjects in comparison with the control group ( p = 0.001). The expression of P53, P21 mRNA was significantly downregulated in the exposed group compared with the healthy nonexposed control group ( p < 0.05). Conversely, the expression of MDM2 and GADD45a did not significantly differ between the exposed subjects and the control group ( p > 0.05). No significant differences were noted between the exposed and control groups regarding the genotype or allele distributions of P53 Arg72Pro polymorphism. These results suggested that chronic exposure to OP insecticides may have mitogenic and carcinogenicity activity for the exposed cases due to downregulation of P53 and P21 but did not demonstrate any DNA damage properties for the exposed cases, and finally, a regular follow-up of the exposed cases for tumor markers is recommended.
Background: At work, farmers are more likely to come into contact with pesticides and other agricultural contaminants. The permanent inhibition of acetylcholinesterase (AChE) at nerve synapses is thought to be a systemic impact of organophosphates (OPs). However, several investigations have shown that AChE inhibition alone does not account for all toxicological effects associated with longterm OP exposure. Although oxidative stress and epigenetic modifications are two of the most recently hypothesized mechanisms, the existence of genetic variations appears to have the greatest influence on biological outcomes. Objectives: The purpose of this study is to investigate the polymorphisms in genes that code for OPs metabolizing enzymes. Because the glutathione-S-transferase (GSTM1) and paraoxonase (PON1) genes encode enzymes that breakdown pesticides with carcinogenic potential, we're particularly interested in them. Methodology: From June to December 2018, a cross-sectional study was done on 24 pesticide applicators and 25 corresponding controls. Serum AChE activities were determined using the EQM Test-Mate kit. Using polymerase chain reaction-restriction fragment length polymorphism, the influence of genetic polymorphism in GSTM1 and PON1 on OPs exposure was examined. Results: Compared to the control group, chronically exposed patients had significantly lower serum AChE enzyme activity (<0.001). In terms of the GSTM1 polymorphism and the R allele of the PON1 (Q192R) polymorphism, there was a significant difference between chronic OP exposed cases and controls. The PON1 (LM) polymorphism was found to be of little consequence. Conclusion: Finally, the GSTM1 and R allele of PON1(LM) polymorphisms may be a risk factor for chronic organophosphates intoxication in Egyptian pesticide applicators.
Background: To examine the histological features of the hamster's submandibular salivary gland following the administration of mepivacaine and articaine as local anaesthetics Objective: The purpose of this study is to assess the anaesthetic effectiveness of both anaesthetics on thyroid hormonal levels and the histopathological changes of the gland. Materials and Methods: Twenty-four male hamsters were divided into three groups. The submandibular glands were removed and preserved in 10% phosphate buffered formalin (PH7.4) for histological investigation, while Group B and C (each of eight animals) received injections of mepivacine and articaine 2% HCl local anaesthetic at a rate of 0.05 ml per second four times after administration. In order to evaluate the amounts of the hormones triiodothyronine (T3) and thyroxin in the blood samples collected (T4) Results: Salivary gland histology using light microscopy revealed normal acini, striated ducts, and glanular ducts in group I, but atrophic changes in serous acini, a loss of acinar architecture, and congestion of inter-acinar blood capillaries in groups II and III, with the latter change being more pronounced in group III as a result of a longer induction period. Long-term use of mepivacaine and articaine medicines results in toxic effects and changes to the salivary glands that indicate stress and damage. When compared to the control, there was a statistically significant rise in T3 and TSH and a substantial drop in T4 in the experimental animals.
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